Materiały źródłowe

• #1

  https://viewpoint.online/handbook/ocular-pathology-atlas/age-related-macular-degeneration/

  Age-related macular degeneration (AMD) is a complex disease with genetic and environmental aetiology and is the leading cause of irreversible blindness. AMD is the maculas degenerative disease, characterized by a loss of visual acuity caused by degeneration of choriocapillaris, retinal pigment epithelium (RPE), and photoreceptors. […] The aetiology of AMD is multifactorial and involves an interplay of genetic, environmental, metabolic, and functional factors, including ageing, family history, smoking, high blood pressure, obesity, hypercholesterolemia, and arteriosclerosis. […] Inflammation, or more specifically, an alternative complement pathway, is at the centre of the pathomechanism of dry age-related macular degeneration. Treatment in the late phase of research is under development. However, a precise mechanism for the disease remains a challenge.

• #2 Age-Related Macular Degeneration (AMD) | Encyclopedia MDPI

  https://encyclopedia.pub/entry/8001

  Age-related macular degeneration (AMD) is a common irreversible sight-threatening disease characterized by progressive degeneration of the central retina, preferentially involving the retinal photoreceptors, the retinal pigment epithelium (RPE), the Bruch’s membrane (BM), or the choroidal microcirculation in the macular region. […] Many risk factors are related to AMD and interact with each other in its pathogenesis, making AMD a complex multifactorial disease. […] Notably, oxidative stress and choroidal vascular dysfunction have been suggested to be the most important trigger factors of AMD pathogenesis. […] It is more and more recognized that genetic risk factors have a critical relevance to the oxidative stress response and choroidal vascular dysfunction in AMD. […] The characteristics of the unique sources of retinal ROS generation and high oxygen consumption suggest that oxidative damage is an essential factor in the mechanism of AMD development.

• #3 Age-Related Macular Degeneration: Epidemiology, Pathophysiology, Diagnosis, and Treatment

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9595233/

  The greatest global root of irremediable amaurosis in the venerable is age-related macular degeneration (AMD), a complex eye condition. […] Age-related cellular and metabolic imbalance are made worse by the creation of excessive amounts of free radical species, which causes mitochondrial malfunction. […] As a result, in AMD-affected eyes, the deprivation of melanocytes, confection, and eventually atrophy within the retinal tissue are caused by the continued proliferation of oxidative stress caused by systemic antioxidant capacity depletion. […] Although substantial research has been done to understand the pathogenesis of AMD’s macular symptoms, the retina’s periphery still needs to be studied extensively. […] The complicated etiology of AMD has been connected to cellular, biochemical, and molecular processes and is impacted by a number of variables, including both environmental influences and genetic predisposition, despite the fact that the pathogenesis of AMD is presently not fully known.

• #4 Age-Related Macular Degeneration: Epidemiology, Pathophysiology, Diagnosis, and Treatment

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9595233/

  Several pathogenic mechanisms can cause AMD at the molecular and biochemical levels, according to our current understanding of the disease. […] As a result, mitochondrial dysfunction, altered proteostasis, altered lipid homeostasis, and lack of cellular control of oxidative stress combine to create an internal feedback loop that leads to the failure of the RPE and the accumulation of abnormal misfolded proteins and abnormal lipids that will eventually form drusen. […] The pathogenesis of AMD includes oxidative stress and retinal inflammatory pathways. […] Neovascular age-related macular degeneration (AMD), sometimes known as wet AMD, is an advanced type of AMD characterized by choroidal neovascularization (CNV), in which newly created blood vessels leak into the retina, producing distortion and fast loss of vision. […] The development of anti-VEGF medications gave people with AMD fresh hope, the necessity of long-term therapy and the frequency of injections place a considerable financial and logistical burden on both individuals and the healthcare system.

• #5 Frontiers | Age-Related Macular Degeneration Revisited: From Pathology and Cellular Stress to Potential Therapies

  https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2020.612812/full

  Despite extensive research, we still do not fully understand critical drivers involved in the initiation of AMD and progression from the early to advanced stages. […] However, breakthroughs in identifying probable pathogenic pathways and molecular mechanisms associated with disease, born out of a consolidation of AMD pathologies, identified through observations of in vivo and ex vivo tissues, epidemiological studies, and in particular high-risk genes linked with AMD development, have been instrumental in the pursuit of animal models and potential therapies. […] These pathways, which are also often related to aging, include but are not limited to: complement activation, lipid trafficking and metabolism, vitamin A cycle/metabolism, proteostasis, bioenergetics, autophagy/mitophagy, extracellular matrix turnover, choroidal vascular dropout, and last but not least oxidant-induced and non-oxidant associated cellular injury and stress.

• #6 Pathogenic Mechanisms

  https://amdbook.org/book/export/html/21

  Age-related changes that predispose to age-related macular degeneration (AMD) occur in the outer retina, more specifically the region that includes the photoreceptors, the RPE, Bruchs membrane and the choriocapillaris. […] The deposition of insoluble material, the calcification and increase in thickness of Bruchs membrane, and a less fenestrated and thinner choriocapillaris leads to photoreceptors/RPE hypoxia. The number of RPE cells reduces with age and in each cell there is a progressive accumulation of lipofuscin during life. Basal laminar and basal linear deposits, drusen, RPE degeneration and atrophy develop and finally, geographic atrophy of RPE and choroidal neovascularization occur. […] Aging is known to be associated with increased oxidative damage and the retina is a fertile environment for reactive oxygen species. Apart from the presence of two retinal blood supplies that generate an highly oxygenated environment, the exposure to high levels of cumulative irradiation, high levels of photosensitizers, large amounts of polyunsaturated fatty acids, readily oxidizable lipid, protein and carbohydrate substrates, and the huge proteolytic burden in the RPE contribute to this particular predisposition to oxidative stress.

• #7 Pathophysiology of AMD: Vision Loss Information | Vision RELIEF

  https://provider-amd.vision-relief.com/pathophysiology-of-amd/

  Age-related macular degeneration (AMD) is a progressively deteriorating eye condition primarily impacting the macula, the central portion of the retina responsible for high-acuity vision. AMD is characterized by the increasing presence and size of drusen, pigmentary changes in the RPE, atrophy of retinal cells, and potentially growth of abnormal blood vessels under the retina, known as choroidal neovascularization. […] While not fully understood, a number of factors are implicated in the pathogenesis of AMD: […] The retina is vulnerable to oxidative damage because of its high oxygen consumption and exposure to light, which leads to the accumulation of such damage and results in cellular dysfunction and death. […] Chronic low-grade inflammation plays a crucial role in AMD progression. This inflammation damages the RPE, photoreceptor cells, and choroidal vessels and may lead to geographic atrophy.

• #8 Mitochondrial Repair in Dry Age-Related Macular Degeneration | Retinal Physician

  https://www.retinalphysician.com/issues/2019/april/mitochondrial-repair-in-dry-age-related-macular-degeneration/

  Age-related macular degeneration (AMD) is considered the leading cause of blindness among elderly people in developed countries. […] there is strong evidence that disruption in major mitochondrial metabolic pathways contributes to AMD pathogenesis. […] Molecular genetic studies have shown that AMD patients can have mtDNA SNP variants in their retinas, some of which cause amino acid changes in the proteins. […] Aging is accompanied by deterioration in mitochondrial structure and a decline in their numbers. […] Interestingly, these abnormalities are in the mtDNA but not the nuclear DNA of RPE cells and correlate with the severity of AMD. […] It has been speculated that damaged mitochondria in AMD can lead to increased superoxide production, which further impairs the proteins, lipids, and DNA, creating a vicious cycle of injury.

• #9 Mitochondrial Repair in Dry Age-Related Macular Degeneration | Retinal Physician

  https://www.retinalphysician.com/issues/2019/april/mitochondrial-repair-in-dry-age-related-macular-degeneration/

  Age-related macular degeneration (AMD) is considered the leading cause of blindness among elderly people in developed countries. […] there is strong evidence that disruption in major mitochondrial metabolic pathways contributes to AMD pathogenesis. […] Molecular genetic studies have shown that AMD patients can have mtDNA SNP variants in their retinas, some of which cause amino acid changes in the proteins. […] Aging is accompanied by deterioration in mitochondrial structure and a decline in their numbers. […] Interestingly, these abnormalities are in the mtDNA but not the nuclear DNA of RPE cells and correlate with the severity of AMD. […] It has been speculated that damaged mitochondria in AMD can lead to increased superoxide production, which further impairs the proteins, lipids, and DNA, creating a vicious cycle of injury.

• #10 Mitochondrial Repair in Dry Age-Related Macular Degeneration | Retinal Physician

  https://www.retinalphysician.com/issues/2019/april/mitochondrial-repair-in-dry-age-related-macular-degeneration/

  Age-related macular degeneration (AMD) is considered the leading cause of blindness among elderly people in developed countries. […] there is strong evidence that disruption in major mitochondrial metabolic pathways contributes to AMD pathogenesis. […] Molecular genetic studies have shown that AMD patients can have mtDNA SNP variants in their retinas, some of which cause amino acid changes in the proteins. […] Aging is accompanied by deterioration in mitochondrial structure and a decline in their numbers. […] Interestingly, these abnormalities are in the mtDNA but not the nuclear DNA of RPE cells and correlate with the severity of AMD. […] It has been speculated that damaged mitochondria in AMD can lead to increased superoxide production, which further impairs the proteins, lipids, and DNA, creating a vicious cycle of injury.

• #11 Age-Related Macular Degeneration: Epidemiology, Pathophysiology, Diagnosis, and Treatment

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9595233/

  The greatest global root of irremediable amaurosis in the venerable is age-related macular degeneration (AMD), a complex eye condition. […] Age-related cellular and metabolic imbalance are made worse by the creation of excessive amounts of free radical species, which causes mitochondrial malfunction. […] As a result, in AMD-affected eyes, the deprivation of melanocytes, confection, and eventually atrophy within the retinal tissue are caused by the continued proliferation of oxidative stress caused by systemic antioxidant capacity depletion. […] Although substantial research has been done to understand the pathogenesis of AMD’s macular symptoms, the retina’s periphery still needs to be studied extensively. […] The complicated etiology of AMD has been connected to cellular, biochemical, and molecular processes and is impacted by a number of variables, including both environmental influences and genetic predisposition, despite the fact that the pathogenesis of AMD is presently not fully known.

• #12

  https://journals.lww.com/md-journal/fulltext/2025/05020/association_between_the_weight_adjusted_waist.30.aspx

  Obesity may lead to secondary hyperlipidemia, increasing the systemic oxidative stress response, and oxidative stress plays a significant role in AMD pathogenesis. […] This study demonstrated that higher WWI levels were associated with an increased risk of AMD, suggesting that managing obesity according to WWI may reduce AMD risk.

• #13 The Role of Inflammation in Age-Related Macular Degeneration

  https://www.ijbs.com/v16p2989.htm

  Current evidence indicated that inflammation plays an integral role in the entire pathogenesis of AMD, especially in CNV or GA. […] We summarize the mechanisms of inflammation-related cytokines and leukocytes, and look forward to getting more inspiration for clinical treatment in AMD. […] In aging eyes, due to the regulation of pro- and anti-inflammatory cytokines by RPE, low-grade chronic inflammation may be induced by these and continue for a long time, and then promote AMD pathogenesis. […] A variety of cytokines have been found to study the relationship between inflammation and the progression of AMD. […] Pro-inflammatory cytokines include IL-1, IL-2, IL-6, IL-8, IL-12, IL-17, TNF-, IFN-, colony-stimulating factor (CSF) -1. […] Evidence has been accumulated that IL-1 induced inflammasome increases the susceptibility of RPE cell to cytotoxicity mediated by photooxidative damage. […] In summary, a series of cytokines play constructive roles in the pathogenesis of AMD, including the formation of CNV and subretinal fibrosis. […] The development of novel targeted therapies could potentially be considered for further investigations.

• #14 The Role of Inflammation in Age-Related Macular Degeneration

  https://www.ijbs.com/v16p2989.htm

  Current evidence indicated that inflammation plays an integral role in the entire pathogenesis of AMD, especially in CNV or GA. […] We summarize the mechanisms of inflammation-related cytokines and leukocytes, and look forward to getting more inspiration for clinical treatment in AMD. […] In aging eyes, due to the regulation of pro- and anti-inflammatory cytokines by RPE, low-grade chronic inflammation may be induced by these and continue for a long time, and then promote AMD pathogenesis. […] A variety of cytokines have been found to study the relationship between inflammation and the progression of AMD. […] Pro-inflammatory cytokines include IL-1, IL-2, IL-6, IL-8, IL-12, IL-17, TNF-, IFN-, colony-stimulating factor (CSF) -1. […] Evidence has been accumulated that IL-1 induced inflammasome increases the susceptibility of RPE cell to cytotoxicity mediated by photooxidative damage. […] In summary, a series of cytokines play constructive roles in the pathogenesis of AMD, including the formation of CNV and subretinal fibrosis. […] The development of novel targeted therapies could potentially be considered for further investigations.

• #15 Age-Related Macular Degeneration – EyeWiki

  https://eyewiki.org/Age-Related_Macular_Degeneration

  The complement system is a three-pronged pathway involved in natural and acquired immunity. […] Activation of the complement system results in cellular damage that is central in the pathogenesis of dry and wet forms of AMD, and this is supported by the presence of many complement system proteins within drusen in patients with AMD. […] In AMD, it is believed that an early „seeding event,” such as an area of retinal pigment epithelium atrophy with cellular debris, induces innate immune system activation at the RPE-choroid-Bruch’s membrane complex. […] Subsequently, complement attack (membrane attack complex activation) leads to collateral damage of retinal tissue. This damage predisposes to geographic atrophy and choroidal neovascular membrane formation.

• #16 Age-Related Macular Degeneration – EyeWiki

  https://eyewiki.org/Age-Related_Macular_Degeneration

  The complement system is a three-pronged pathway involved in natural and acquired immunity. […] Activation of the complement system results in cellular damage that is central in the pathogenesis of dry and wet forms of AMD, and this is supported by the presence of many complement system proteins within drusen in patients with AMD. […] In AMD, it is believed that an early „seeding event,” such as an area of retinal pigment epithelium atrophy with cellular debris, induces innate immune system activation at the RPE-choroid-Bruch’s membrane complex. […] Subsequently, complement attack (membrane attack complex activation) leads to collateral damage of retinal tissue. This damage predisposes to geographic atrophy and choroidal neovascular membrane formation.

• #17 Age-Related Macular Degeneration – EyeWiki

  https://eyewiki.org/Age-Related_Macular_Degeneration

  The complement system is a three-pronged pathway involved in natural and acquired immunity. […] Activation of the complement system results in cellular damage that is central in the pathogenesis of dry and wet forms of AMD, and this is supported by the presence of many complement system proteins within drusen in patients with AMD. […] In AMD, it is believed that an early „seeding event,” such as an area of retinal pigment epithelium atrophy with cellular debris, induces innate immune system activation at the RPE-choroid-Bruch’s membrane complex. […] Subsequently, complement attack (membrane attack complex activation) leads to collateral damage of retinal tissue. This damage predisposes to geographic atrophy and choroidal neovascular membrane formation.

• #18 Age-Related Macular Degeneration – EyeWiki

  https://eyewiki.org/Age-Related_Macular_Degeneration

  The complement system is a three-pronged pathway involved in natural and acquired immunity. […] Activation of the complement system results in cellular damage that is central in the pathogenesis of dry and wet forms of AMD, and this is supported by the presence of many complement system proteins within drusen in patients with AMD. […] In AMD, it is believed that an early „seeding event,” such as an area of retinal pigment epithelium atrophy with cellular debris, induces innate immune system activation at the RPE-choroid-Bruch’s membrane complex. […] Subsequently, complement attack (membrane attack complex activation) leads to collateral damage of retinal tissue. This damage predisposes to geographic atrophy and choroidal neovascular membrane formation.

• #19 Age-Related Macular Degeneration – EyeWiki

  https://eyewiki.org/Age-Related_Macular_Degeneration

  The complement system is a three-pronged pathway involved in natural and acquired immunity. […] Activation of the complement system results in cellular damage that is central in the pathogenesis of dry and wet forms of AMD, and this is supported by the presence of many complement system proteins within drusen in patients with AMD. […] In AMD, it is believed that an early „seeding event,” such as an area of retinal pigment epithelium atrophy with cellular debris, induces innate immune system activation at the RPE-choroid-Bruch’s membrane complex. […] Subsequently, complement attack (membrane attack complex activation) leads to collateral damage of retinal tissue. This damage predisposes to geographic atrophy and choroidal neovascular membrane formation.

• #20 A systems biology approach towards understanding and treating non-neovascular age-related macular degeneration | Nature Communications

  https://www.nature.com/articles/s41467-019-11262-1

  The intention is to raise awareness of the impact of AMD on public health, review the current understanding of the pathobiology of this disease, offer future research directions that focus on unbiased systems approaches, encourage the continued efforts of dedicated vision scientists who focus on dry AMD, and encourage the broader scientific community to join in a collaborative effort to develop therapies for this complex and debilitating disease. […] The hallmarks of immune activation include drusen formation, subretinal and choroidal recruitment of microglia/macrophages, mast cell activation, and RPE immune activation. […] Genetic studies have identified complement pathway gene variants with AMD risk, which strongly implicates the complement pathway in driving AMD progression. […] In dry AMD, RPE mitochondrial mass is reduced, mitochondria are morphologically abnormal, and mitochondrial DNA (mtDNA) damage increases with disease severity.

• #21 Macular degeneration – Wikipedia

  https://en.wikipedia.org/wiki/Macular_degeneration

  In the wet (exudative) form, which is more severe, blood vessels grow up from the choroid (neovascularization) behind the retina which can leak exudate and fluid and also cause hemorrhaging. […] Early work demonstrated a family of immune mediators was plentiful in drusen. […] Complement factor H (CFH) is an important inhibitor of this inflammatory cascade, and a disease-associated polymorphism in the CFH gene strongly associates with AMD. […] Thus an AMD pathophysiological model of chronic low grade complement activation and inflammation in the macula has been advanced. […] A powerful predictor of AMD is found on chromosome 10q26 at LOC 387715. […] Other gene markers of progression risk includes tissue inhibitor of metalloproteinase 3 (TIMP3), suggesting a role for extracellular matrix metabolism in AMD progression. […] The early stigmata of the disease, drusen, are rich in cholesterol, offering face validity to the results of genome-wide association studies.

• #22 Mitochondrial Repair in Dry Age-Related Macular Degeneration | Retinal Physician

  https://www.retinalphysician.com/issues/2019/april/mitochondrial-repair-in-dry-age-related-macular-degeneration/

  The risk allele for complement factor H, regulator of the alternative complement pathway, increases the risk of mtDNA damage. […] Antioxidant agents, such as alpha-lipoic acid, alpha-tocopherol, genistein, resveratrol, memantine, MitoQ, and Mito-CP, may preserve mitochondrial function by decelerating the progression to blindness in AMD patients. […] Mitochondria-targeting drugs present great potential for future interventions in patients with dry AMD.

• #23

  https://viewpoint.online/handbook/ocular-pathology-atlas/age-related-macular-degeneration/

  The hallmark of the disease is the presence of drusen. […] Drusen are focal deposits of extracellular debris that typically form between the basal lamina of the RPE and the inner collagenous layer of Bruchs membrane. Broadly speaking, the disease has two major subtypes: a non-exudative or so-called dry type and an exudative or so-called wet type. […] Classical drusen are located below the retinal pigment epithelium (RPE). However, small drusenoid deposits may be located above the RPE and are called subretinal drusenoid deposits or pseudodrusen. Those deposits are also a risk factor for the development of late stages of AMD (geographic atrophy and type 3 CNV in exudative AMD). […] Geographic atrophy is characterized by a local and sharp demarcation of atrophic outer retinal, RPE, and choriocapillaris layers. Large choroidal vessels are seen at the area of atrophies. It starts in the perifoveal region and progresses towards the fovea. It is bilateral but, in most cases, asymmetrical. Likewise, it may represent a single or multifocal.

• #24

  https://viewpoint.online/handbook/ocular-pathology-atlas/age-related-macular-degeneration/

  The hallmark of the disease is the presence of drusen. […] Drusen are focal deposits of extracellular debris that typically form between the basal lamina of the RPE and the inner collagenous layer of Bruchs membrane. Broadly speaking, the disease has two major subtypes: a non-exudative or so-called dry type and an exudative or so-called wet type. […] Classical drusen are located below the retinal pigment epithelium (RPE). However, small drusenoid deposits may be located above the RPE and are called subretinal drusenoid deposits or pseudodrusen. Those deposits are also a risk factor for the development of late stages of AMD (geographic atrophy and type 3 CNV in exudative AMD). […] Geographic atrophy is characterized by a local and sharp demarcation of atrophic outer retinal, RPE, and choriocapillaris layers. Large choroidal vessels are seen at the area of atrophies. It starts in the perifoveal region and progresses towards the fovea. It is bilateral but, in most cases, asymmetrical. Likewise, it may represent a single or multifocal.

• #25 Macular degeneration – Wikipedia

  https://en.wikipedia.org/wiki/Macular_degeneration

  In the wet (exudative) form, which is more severe, blood vessels grow up from the choroid (neovascularization) behind the retina which can leak exudate and fluid and also cause hemorrhaging. […] Early work demonstrated a family of immune mediators was plentiful in drusen. […] Complement factor H (CFH) is an important inhibitor of this inflammatory cascade, and a disease-associated polymorphism in the CFH gene strongly associates with AMD. […] Thus an AMD pathophysiological model of chronic low grade complement activation and inflammation in the macula has been advanced. […] A powerful predictor of AMD is found on chromosome 10q26 at LOC 387715. […] Other gene markers of progression risk includes tissue inhibitor of metalloproteinase 3 (TIMP3), suggesting a role for extracellular matrix metabolism in AMD progression. […] The early stigmata of the disease, drusen, are rich in cholesterol, offering face validity to the results of genome-wide association studies.

• #26 Age Related Macular Degeneration: a Complex Pathology

  https://austinpublishinggroup.com/genetics-genomic-research/fulltext/ajggr-v1-id1005.php

  An increased level of HTRA1 is suggested to play a potential role in the pathogenesis of AMD. […] In recent years, numerous clinical-genetic studies documented the crucial role of inflammation and immune-mediated processes (e.g. complement activation) in the pathogenesis of AMD. […] The hallmark of AMD, „drusen”, contains large amount of components involved in the complement pathway. […] The accumulation of macrophages in the AMD tissues suggest an important role for macrophages in AMD pathogenesis, which is well supported in AMD animal model studies. […] The precise roles and impacts of macrophages in AMD are unclear and debated in the AMD field. […] The autophagy processes are highly active in the RPE layer because RPE cells are subject to oxidative stress, high oxygen tension, lifelong light illumination, and are involve in daily phagocytosis of photoreceptor outer segments.

• #27 Pathophysiology of AMD: Vision Loss Information | Vision RELIEF

  https://provider-amd.vision-relief.com/pathophysiology-of-amd/

  Drusen play a role in inhibiting the transport of metabolites to the choroid vessels and their molecular components also initiate inflammation through the complement cascade. […] Age-related changes in the RPE cells lead to decreased efficiency in maintaining photoreceptor health. […] Several genetic variants, particularly those that regulate inflammation, lipid metabolism, and age-related maculopathy susceptibility 2 (ARMS2 or LOC387715) and high-temperature requirement A-serine peptidase 1 (HTRA1) genes are implicated in the development and progression of AMD. […] nAMD is characterized by abnormal angiogenesis within the choroid, subretinal space, and retina, driven by angiogenic signaling molecules, including vascular epithelial growth factor (VEGF). Continued damage to the RPE leads to further dysfunction of Bruch’s membrane, which in some patients, is accompanied by a rise in VEGF, resulting in the growth of new vessels under the retinal pigment epithelium and the retina.

• #28 The Age-Related Macular Degeneration (AMD)-Preventing Mechanism of Natural Products

  https://www.mdpi.com/2227-9717/10/4/678

  Age-related macular degeneration (AMD) is related to central visual loss in elderly people and, based on the increment in the percentage of the aging population, the number of people suffering from AMD could increase. AMD is initiated by retinal pigment epithelium (RPE) cell death, finally leading to neovascularization in the macula lutea. RPE death (apoptosis) increases AMD severity, as it makes it difficult to supply nutrition and to exchange gases. The important pathogenic factors of AMD are bis-retinoid N-retinyl-N-retinylidene ethanolamine (A2E), especially A2E-epoxides and blue light (in the wavelength range of 480 ± 20 nm). A2E is a very unstable pigment, which easily changes to its oxidized form (A2E-epoxide) and, during A2E oxidization, many reactive oxygen species (ROSs) are produced. A2E can be changed to A2E-epoxide by blue light, and, at the same time, many ROS, such as H2O2, O2−, and OH·, can be synthesized and start the oxidization of RPEs, thus destroying them. Accumulated drusen not only induces central region blindness, but also stimulates inflammation in RPE, and the exacerbation of an inflammatory response is a trigger of AMD occurrence. The oxidative stress is closely connected with inflammation, and, in particular, A2E stimulates RPE cell inflammation by increasing the level of IL-1β via the NLRP3 inflammasome. Carbonyl stress means that, without the oxidative stress during the Maillard reaction, carbonylated products, such as malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), and 4-hydroxyhexanal (4-HHE), are synthesized from some compounds, such as lipids, protein, and DNA, via carbonylation. From the toxicological point of view, although each type of stress can induce RPE cells to be damaged by itself, all of them participate via their toxicological network in AMD occurrence via RPE cell apoptosis. AMD is initiated by RPE cell death and, as it is difficult to supply blood to photoreceptors, angiogenesis finally occurs from the choroid vessel to photoreceptors. RPE cell death is related to oxidative stress, inflammatory stress, and carbonyl stress, and although each type of stress is harmful to cells, all three stresses influence RPE cell death as all occur simultaneously.

• #29 Age-Related Macular Degeneration: From One Medical Student to Another. EyeRounds :: The University of Iowa, Ophthalmology

  https://webeye.ophth.uiowa.edu/eyeforum/tutorials/AMD-medical-student/index.htm

  Age-Related Macular Degeneration (AMD) is the most common cause of blindness in the Western world. […] The pathogenesis of AMD is not completely clear. Scientists feel that AMD is likely a pathological extension of normal aging that occurs within the eye. It does not appear that there is one mechanism that causes AMD, but that it stems from a collection of complex processes that combine to create the disease state with age. However, it is clear that both genetics and the environment play a role in the pathogenesis. […] Bruchs membrane plays a critical role in the pathogenesis of AMD. In young, healthy eyes, Bruchs membrane functions as a structural support that is permeable to fluid and small molecules, such as oxygen and glucose. It also acts as a barrier against neovascularization by containing molecules in the elastin layer that are anti-angiogenic.

• #30 Age-Related Macular Degeneration: From One Medical Student to Another. EyeRounds :: The University of Iowa, Ophthalmology

  https://webeye.ophth.uiowa.edu/eyeforum/tutorials/AMD-medical-student/index.htm

  As we age, Bruchs membrane tends to accumulate debris in the elastin lamina and also drusen between the collagen layer and RPE basal lamina. This debris accumulation causes a reduction in the permeability of Bruchs membrane. This will hinder the pumping of waste from inside to outside of the eye by the RPE and may cause pigment epithelial detachments. […] Aging is also associated with thinning and breakdown of the central elastin layer within Bruchs membrane. Thinning of this layer increases the risk of neovascularization as it reduces the number of bound anti-angiogenic proteins. In addition, elastin breakdown products (elastin-derived proteins) are themselves angiogenic. Therefore, breakdown of elastin in Bruchs membrane not only causes a reduction in the barrier to neovascularization, but also stimulates vessel growth.

• #31 Age-Related Macular Degeneration: From One Medical Student to Another. EyeRounds :: The University of Iowa, Ophthalmology

  https://webeye.ophth.uiowa.edu/eyeforum/tutorials/AMD-medical-student/index.htm

  As we age, Bruchs membrane tends to accumulate debris in the elastin lamina and also drusen between the collagen layer and RPE basal lamina. This debris accumulation causes a reduction in the permeability of Bruchs membrane. This will hinder the pumping of waste from inside to outside of the eye by the RPE and may cause pigment epithelial detachments. […] Aging is also associated with thinning and breakdown of the central elastin layer within Bruchs membrane. Thinning of this layer increases the risk of neovascularization as it reduces the number of bound anti-angiogenic proteins. In addition, elastin breakdown products (elastin-derived proteins) are themselves angiogenic. Therefore, breakdown of elastin in Bruchs membrane not only causes a reduction in the barrier to neovascularization, but also stimulates vessel growth.

• #32 Pathogenesis and Pathophysiology of Age-Related Macular Degeneration | Ento Key

  https://entokey.com/pathogenesis-and-pathophysiology-of-age-related-macular-degeneration/

  Pathogenesis and Pathophysiology of Age-Related Macular Degeneration […] The pathophysiology of AMD is incompletely understood, but genetic tools offer new insights into the development and progress of AMD. […] Most of the authors defend the theory in which AMD is an advanced stage or perturbation of the normal process of eye senescence. […] The pathology of AMD is characterized by degenerative changes affecting outer retina (photoreceptors), RPE, BrM, and choriocapillaris. […] The RPE is a central element in the pathogenesis of AMD. […] Another pivotal function of the RPE is light absorption and protection against photo-oxidation. […] The RPE absorbs glucose, retinol, ascorbic acid, and fatty acids in the blood and delivers them to the photoreceptor. […] The delivery of the fatty acids such as docosahexaenoic acid and eicosapentaenoic acid to the photoreceptor is another important RPE function.

• #33 Mechanisms of age-related macular degeneration

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3404137/

  The RPE integrates numerous stimuli to define its own health, while also receiving and broadcasting signals to and from the retinal microenvironment. […] The critical event in AMD pathogenesis, from which there is no return, is RPE dysfunction and degeneration. […] An important route of communication and recurring theme in AMD pathology is the crosstalk of RPE with immune and vascular systems. […] The potential for immune contribution to CNV begs several salient questions about disease mechanism. […] The activity of the enzyme DICER1 is sufficiently broad-reaching that it is an attractive candidate as a choreographer of retinal health and homeostasis. […] The cumulative burden on the RPE may, or may not, converge to a single pathway that determines RPE cell viability. […] The mechanistic role of DICER1 and Alu RNA in AMD are deciphered, neutralization of Alu RNA (e.g. antisense oligonucleotides), restoration of DICER1 levels (e.g. gene replacement therapy), or pharmacological targeting of the downstream MyD88 effector (e.g. small molecule or siRNA) are possible strategies to address this imbalance in AMD pathophysiology.

• #34 Mechanisms of age-related macular degeneration

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3404137/

  The RPE integrates numerous stimuli to define its own health, while also receiving and broadcasting signals to and from the retinal microenvironment. […] The critical event in AMD pathogenesis, from which there is no return, is RPE dysfunction and degeneration. […] An important route of communication and recurring theme in AMD pathology is the crosstalk of RPE with immune and vascular systems. […] The potential for immune contribution to CNV begs several salient questions about disease mechanism. […] The activity of the enzyme DICER1 is sufficiently broad-reaching that it is an attractive candidate as a choreographer of retinal health and homeostasis. […] The cumulative burden on the RPE may, or may not, converge to a single pathway that determines RPE cell viability. […] The mechanistic role of DICER1 and Alu RNA in AMD are deciphered, neutralization of Alu RNA (e.g. antisense oligonucleotides), restoration of DICER1 levels (e.g. gene replacement therapy), or pharmacological targeting of the downstream MyD88 effector (e.g. small molecule or siRNA) are possible strategies to address this imbalance in AMD pathophysiology.

• #35 Pathogenesis and Pathophysiology of Age-Related Macular Degeneration | Ento Key

  https://entokey.com/pathogenesis-and-pathophysiology-of-age-related-macular-degeneration/

  Pathogenesis and Pathophysiology of Age-Related Macular Degeneration […] The pathophysiology of AMD is incompletely understood, but genetic tools offer new insights into the development and progress of AMD. […] Most of the authors defend the theory in which AMD is an advanced stage or perturbation of the normal process of eye senescence. […] The pathology of AMD is characterized by degenerative changes affecting outer retina (photoreceptors), RPE, BrM, and choriocapillaris. […] The RPE is a central element in the pathogenesis of AMD. […] Another pivotal function of the RPE is light absorption and protection against photo-oxidation. […] The RPE absorbs glucose, retinol, ascorbic acid, and fatty acids in the blood and delivers them to the photoreceptor. […] The delivery of the fatty acids such as docosahexaenoic acid and eicosapentaenoic acid to the photoreceptor is another important RPE function.

• #36 Pathogenesis and Pathophysiology of Age-Related Macular Degeneration | Ento Key

  https://entokey.com/pathogenesis-and-pathophysiology-of-age-related-macular-degeneration/

  Pathogenesis and Pathophysiology of Age-Related Macular Degeneration […] The pathophysiology of AMD is incompletely understood, but genetic tools offer new insights into the development and progress of AMD. […] Most of the authors defend the theory in which AMD is an advanced stage or perturbation of the normal process of eye senescence. […] The pathology of AMD is characterized by degenerative changes affecting outer retina (photoreceptors), RPE, BrM, and choriocapillaris. […] The RPE is a central element in the pathogenesis of AMD. […] Another pivotal function of the RPE is light absorption and protection against photo-oxidation. […] The RPE absorbs glucose, retinol, ascorbic acid, and fatty acids in the blood and delivers them to the photoreceptor. […] The delivery of the fatty acids such as docosahexaenoic acid and eicosapentaenoic acid to the photoreceptor is another important RPE function.

• #37 Pathophysiology of AMD: Vision Loss Information | Vision RELIEF

  https://provider-amd.vision-relief.com/pathophysiology-of-amd/

  Drusen play a role in inhibiting the transport of metabolites to the choroid vessels and their molecular components also initiate inflammation through the complement cascade. […] Age-related changes in the RPE cells lead to decreased efficiency in maintaining photoreceptor health. […] Several genetic variants, particularly those that regulate inflammation, lipid metabolism, and age-related maculopathy susceptibility 2 (ARMS2 or LOC387715) and high-temperature requirement A-serine peptidase 1 (HTRA1) genes are implicated in the development and progression of AMD. […] nAMD is characterized by abnormal angiogenesis within the choroid, subretinal space, and retina, driven by angiogenic signaling molecules, including vascular epithelial growth factor (VEGF). Continued damage to the RPE leads to further dysfunction of Bruch’s membrane, which in some patients, is accompanied by a rise in VEGF, resulting in the growth of new vessels under the retinal pigment epithelium and the retina.

• #38 Age-Related Macular Degeneration (AMD): Pathophysiology, Drug Targeting Approaches, and Recent Developments in Nanotherapeutics

  https://www.mdpi.com/1648-9144/60/10/1647

  It is the first major review that will cover various topics including etiology, Types and Symptoms, prevalence and risk factors; pathogenesis focusing on molecular aspects, particularly inflammatory, oxidative, and angiogenesis aspects; therapeutic intervention in AMD; strategic drug delivery approaches. […] The AMD is a catastrophic eye illness that damages the macula, the key region of the retina accountable for clear and sharp vision. […] Age-related changes in the eye are often initiated by the accumulation of uncleared cellular debris (drusen a clinical hallmark of AMD) originating from the retinal pigmented epithelium (RPE) in the region of interface between RPE, Bruch’s membrane, and the choroid. […] An extracellular matrix with many layers, known as Bruch’s membrane, functions as a barrier against pathological processes like choroidal neovascularization (CNV) and as a physical and biochemical support system for normal physiological activities.

• #39 The Age-Related Macular Degeneration (AMD)-Preventing Mechanism of Natural Products

  https://www.mdpi.com/2227-9717/10/4/678

  Age-related macular degeneration (AMD) is related to central visual loss in elderly people and, based on the increment in the percentage of the aging population, the number of people suffering from AMD could increase. AMD is initiated by retinal pigment epithelium (RPE) cell death, finally leading to neovascularization in the macula lutea. RPE death (apoptosis) increases AMD severity, as it makes it difficult to supply nutrition and to exchange gases. The important pathogenic factors of AMD are bis-retinoid N-retinyl-N-retinylidene ethanolamine (A2E), especially A2E-epoxides and blue light (in the wavelength range of 480 ± 20 nm). A2E is a very unstable pigment, which easily changes to its oxidized form (A2E-epoxide) and, during A2E oxidization, many reactive oxygen species (ROSs) are produced. A2E can be changed to A2E-epoxide by blue light, and, at the same time, many ROS, such as H2O2, O2−, and OH·, can be synthesized and start the oxidization of RPEs, thus destroying them. Accumulated drusen not only induces central region blindness, but also stimulates inflammation in RPE, and the exacerbation of an inflammatory response is a trigger of AMD occurrence. The oxidative stress is closely connected with inflammation, and, in particular, A2E stimulates RPE cell inflammation by increasing the level of IL-1β via the NLRP3 inflammasome. Carbonyl stress means that, without the oxidative stress during the Maillard reaction, carbonylated products, such as malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), and 4-hydroxyhexanal (4-HHE), are synthesized from some compounds, such as lipids, protein, and DNA, via carbonylation. From the toxicological point of view, although each type of stress can induce RPE cells to be damaged by itself, all of them participate via their toxicological network in AMD occurrence via RPE cell apoptosis. AMD is initiated by RPE cell death and, as it is difficult to supply blood to photoreceptors, angiogenesis finally occurs from the choroid vessel to photoreceptors. RPE cell death is related to oxidative stress, inflammatory stress, and carbonyl stress, and although each type of stress is harmful to cells, all three stresses influence RPE cell death as all occur simultaneously.

• #40 Age-Related Macular Degeneration (AMD): Pathophysiology, Drug Targeting Approaches, and Recent Developments in Nanotherapeutics

  https://www.mdpi.com/1648-9144/60/10/1647

  This process along with concomitant processes such as oxidative stress, angiogenesis, inflammation, and activation of complement cascade results in reduced permeability of thickened Bruch’s membrane culminating in reduction of transport of nutrients to RPE and waste product to choroid in addition to reduced choroidal vasculature. […] The difference between the tissues’ generation of reactive oxygen species (ROS) and their capacity to remove these ROS from the body and repair the damage they have caused is known as oxidative stress. […] It has been proved that oxidative stress in AMD damages the RPE, a layer of cells that supports the unique function of photoreceptor cells in the retina. […] Moreover, inflammation brought on by oxidative stress is believed to have a role in the advancement of AMD.

• #41 Age-Related Macular Degeneration (AMD): Pathophysiology, Drug Targeting Approaches, and Recent Developments in Nanotherapeutics

  https://www.mdpi.com/1648-9144/60/10/1647

  Angiogenesis plays a crucial part in AMD’s progression from the disease’s early (dry form) to its later, more severe (wet form). […] The development of these malformed blood vessels is fuelled by VEGF, which is produced in response to ischemia (lack of oxygen) and other factors such as inflammation. […] Furthermore, it is thought that the presence of large drusen deposits initiates the conversion process by causing complement activation and VEGF and Platelet-derived growth factor (PDGF) secretion. […] The complexity of AMD pathogenesis and pathophysiology is responsible for the lack of fully effective therapeutic options. […] The pathophysiology of AMD is significantly influenced by the functional aberrations of the complement system. […] A highly activated complement system has been reported to be present in patients with intermediate and final stages of dry AMD.

• #42 Age-Related Macular Degeneration (AMD): Pathophysiology, Drug Targeting Approaches, and Recent Developments in Nanotherapeutics

  https://www.mdpi.com/1648-9144/60/10/1647

  Angiogenesis plays a crucial part in AMD’s progression from the disease’s early (dry form) to its later, more severe (wet form). […] The development of these malformed blood vessels is fuelled by VEGF, which is produced in response to ischemia (lack of oxygen) and other factors such as inflammation. […] Furthermore, it is thought that the presence of large drusen deposits initiates the conversion process by causing complement activation and VEGF and Platelet-derived growth factor (PDGF) secretion. […] The complexity of AMD pathogenesis and pathophysiology is responsible for the lack of fully effective therapeutic options. […] The pathophysiology of AMD is significantly influenced by the functional aberrations of the complement system. […] A highly activated complement system has been reported to be present in patients with intermediate and final stages of dry AMD.

• #43 Age-Related Macular Degeneration (AMD): Pathophysiology, Drug Targeting Approaches, and Recent Developments in Nanotherapeutics

  https://www.mdpi.com/1648-9144/60/10/1647

  Angiogenesis plays a crucial part in AMD’s progression from the disease’s early (dry form) to its later, more severe (wet form). […] The development of these malformed blood vessels is fuelled by VEGF, which is produced in response to ischemia (lack of oxygen) and other factors such as inflammation. […] Furthermore, it is thought that the presence of large drusen deposits initiates the conversion process by causing complement activation and VEGF and Platelet-derived growth factor (PDGF) secretion. […] The complexity of AMD pathogenesis and pathophysiology is responsible for the lack of fully effective therapeutic options. […] The pathophysiology of AMD is significantly influenced by the functional aberrations of the complement system. […] A highly activated complement system has been reported to be present in patients with intermediate and final stages of dry AMD.

• #44 Age-Related Macular Degeneration (AMD): Pathophysiology, Drug Targeting Approaches, and Recent Developments in Nanotherapeutics

  https://www.mdpi.com/1648-9144/60/10/1647

  Angiogenesis plays a crucial part in AMD’s progression from the disease’s early (dry form) to its later, more severe (wet form). […] The development of these malformed blood vessels is fuelled by VEGF, which is produced in response to ischemia (lack of oxygen) and other factors such as inflammation. […] Furthermore, it is thought that the presence of large drusen deposits initiates the conversion process by causing complement activation and VEGF and Platelet-derived growth factor (PDGF) secretion. […] The complexity of AMD pathogenesis and pathophysiology is responsible for the lack of fully effective therapeutic options. […] The pathophysiology of AMD is significantly influenced by the functional aberrations of the complement system. […] A highly activated complement system has been reported to be present in patients with intermediate and final stages of dry AMD.

• #45 Age-Related Macular Degeneration: Epidemiology, Pathophysiology, Diagnosis, and Treatment

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9595233/

  Several pathogenic mechanisms can cause AMD at the molecular and biochemical levels, according to our current understanding of the disease. […] As a result, mitochondrial dysfunction, altered proteostasis, altered lipid homeostasis, and lack of cellular control of oxidative stress combine to create an internal feedback loop that leads to the failure of the RPE and the accumulation of abnormal misfolded proteins and abnormal lipids that will eventually form drusen. […] The pathogenesis of AMD includes oxidative stress and retinal inflammatory pathways. […] Neovascular age-related macular degeneration (AMD), sometimes known as wet AMD, is an advanced type of AMD characterized by choroidal neovascularization (CNV), in which newly created blood vessels leak into the retina, producing distortion and fast loss of vision. […] The development of anti-VEGF medications gave people with AMD fresh hope, the necessity of long-term therapy and the frequency of injections place a considerable financial and logistical burden on both individuals and the healthcare system.

• #46 The Role of Inflammation in Age-Related Macular Degeneration

  https://www.ijbs.com/v16p2989.htm

  Age-related macular degeneration (AMD) is a blinding eye disease which incidence gradually increases with age. Inflammation participates in AMD pathogenesis, including choroidal neovascularization and geographic atrophy. […] In this review, we summarize and discuss the role and mechanism(s) of inflammation, as well as inflammatory cytokines and leukocytes in the pathogenesis of AMD. […] AMD is the consequence of a multifactorial interaction of metabolism, functions, genetics and the environment, and these multiple factors foster a stage conducive for the chronic structural changes in the macular area (choriocapillaries, Bruch’s membrane (BM), RPE, photoreceptor). […] Thus, inflammation is believed to play indispensable roles in the pathogenesis of both dry and wet AMD. […] The occurrence of CNV is the main feature of nAMD, which is associated with inflammatory cytokines, complement system activation, and promotion/inhibition of macrophages/microglia. […] Therefore, it is speculated that inflammation plays different roles in the pathogenesis of wet and dry AMD, respectively.

• #47 Macular degeneration – Wikipedia

  https://en.wikipedia.org/wiki/Macular_degeneration

  In the wet (exudative) form, which is more severe, blood vessels grow up from the choroid (neovascularization) behind the retina which can leak exudate and fluid and also cause hemorrhaging. […] Early work demonstrated a family of immune mediators was plentiful in drusen. […] Complement factor H (CFH) is an important inhibitor of this inflammatory cascade, and a disease-associated polymorphism in the CFH gene strongly associates with AMD. […] Thus an AMD pathophysiological model of chronic low grade complement activation and inflammation in the macula has been advanced. […] A powerful predictor of AMD is found on chromosome 10q26 at LOC 387715. […] Other gene markers of progression risk includes tissue inhibitor of metalloproteinase 3 (TIMP3), suggesting a role for extracellular matrix metabolism in AMD progression. […] The early stigmata of the disease, drusen, are rich in cholesterol, offering face validity to the results of genome-wide association studies.

• #48 Novel treatments and genetics of age-related macular degeneration-a narrative review – Arabi – Annals of Eye Science

  https://aes.amegroups.org/article/view/6375/html

  Age-related macular degeneration (AMD) remains a leading cause of severe visual impairment in developing countries. […] Recent advances in AMD genetics have provided new insights into the pathogenesis and novel therapeutic targets of AMD, but the benefits of using genetic testing and genotype-based risk models for AMD development and progression still lacks evidence. […] AMD is a complex disease, and several genetic variants and environmental factors contribute to the pathogenesis of disease. […] The presence of multiple genes involved in AMD and incomplete knowledge of genetic pathogenesis have made American Academy of Ophthalmology to recommend avoiding routine genetic testing. […] Although several mediators are involved in the pathogenesis of AMD, VEGF pathways remain to be the main target of gene therapy for AMD.

• #49 Pathophysiology of AMD: Vision Loss Information | Vision RELIEF

  https://provider-amd.vision-relief.com/pathophysiology-of-amd/

  Drusen play a role in inhibiting the transport of metabolites to the choroid vessels and their molecular components also initiate inflammation through the complement cascade. […] Age-related changes in the RPE cells lead to decreased efficiency in maintaining photoreceptor health. […] Several genetic variants, particularly those that regulate inflammation, lipid metabolism, and age-related maculopathy susceptibility 2 (ARMS2 or LOC387715) and high-temperature requirement A-serine peptidase 1 (HTRA1) genes are implicated in the development and progression of AMD. […] nAMD is characterized by abnormal angiogenesis within the choroid, subretinal space, and retina, driven by angiogenic signaling molecules, including vascular epithelial growth factor (VEGF). Continued damage to the RPE leads to further dysfunction of Bruch’s membrane, which in some patients, is accompanied by a rise in VEGF, resulting in the growth of new vessels under the retinal pigment epithelium and the retina.

• #50 Macular degeneration – Wikipedia

  https://en.wikipedia.org/wiki/Macular_degeneration

  In the wet (exudative) form, which is more severe, blood vessels grow up from the choroid (neovascularization) behind the retina which can leak exudate and fluid and also cause hemorrhaging. […] Early work demonstrated a family of immune mediators was plentiful in drusen. […] Complement factor H (CFH) is an important inhibitor of this inflammatory cascade, and a disease-associated polymorphism in the CFH gene strongly associates with AMD. […] Thus an AMD pathophysiological model of chronic low grade complement activation and inflammation in the macula has been advanced. […] A powerful predictor of AMD is found on chromosome 10q26 at LOC 387715. […] Other gene markers of progression risk includes tissue inhibitor of metalloproteinase 3 (TIMP3), suggesting a role for extracellular matrix metabolism in AMD progression. […] The early stigmata of the disease, drusen, are rich in cholesterol, offering face validity to the results of genome-wide association studies.

• #51 Macular degeneration – Wikipedia

  https://en.wikipedia.org/wiki/Macular_degeneration

  In the wet (exudative) form, which is more severe, blood vessels grow up from the choroid (neovascularization) behind the retina which can leak exudate and fluid and also cause hemorrhaging. […] Early work demonstrated a family of immune mediators was plentiful in drusen. […] Complement factor H (CFH) is an important inhibitor of this inflammatory cascade, and a disease-associated polymorphism in the CFH gene strongly associates with AMD. […] Thus an AMD pathophysiological model of chronic low grade complement activation and inflammation in the macula has been advanced. […] A powerful predictor of AMD is found on chromosome 10q26 at LOC 387715. […] Other gene markers of progression risk includes tissue inhibitor of metalloproteinase 3 (TIMP3), suggesting a role for extracellular matrix metabolism in AMD progression. […] The early stigmata of the disease, drusen, are rich in cholesterol, offering face validity to the results of genome-wide association studies.

• #52 Age-Related Macular Degeneration – EyeWiki

  https://eyewiki.org/Age-Related_Macular_Degeneration

  The degenerating retina succumbs to the final end point of geographic atrophy, choroidal neovascularization and pigment epithelial detachment. […] Treatments targeting intermediate disease mechanisms or initiating disease factors are in the minority, but may offer a more successful approach to vision preservation than those targeting relatively later steps in AMD pathophysiology (i.e., choroidal neovascularization). […] Biochemical pathways and genetic association studies have shed light on the possible biochemical pathways that go awry in AMD. […] Two polymorphisms, Tyr402His at 10q26 (Complement factor H locus), and Ala69Ser (LOC387715) may be responsible for up to 50-75% of the genetic risk of AMD. […] Aside from explaining some of the genetic predisposition in AMD, these loci have uncovered new biochemical pathways hitherto unlinked to AMD pathogenesis, providing novel therapeutic targets.

• #53 Age-Related Macular Degeneration – EyeWiki

  https://eyewiki.org/Age-Related_Macular_Degeneration

  The degenerating retina succumbs to the final end point of geographic atrophy, choroidal neovascularization and pigment epithelial detachment. […] Treatments targeting intermediate disease mechanisms or initiating disease factors are in the minority, but may offer a more successful approach to vision preservation than those targeting relatively later steps in AMD pathophysiology (i.e., choroidal neovascularization). […] Biochemical pathways and genetic association studies have shed light on the possible biochemical pathways that go awry in AMD. […] Two polymorphisms, Tyr402His at 10q26 (Complement factor H locus), and Ala69Ser (LOC387715) may be responsible for up to 50-75% of the genetic risk of AMD. […] Aside from explaining some of the genetic predisposition in AMD, these loci have uncovered new biochemical pathways hitherto unlinked to AMD pathogenesis, providing novel therapeutic targets.

• #54 Tissue engineering in age-related macular degeneration: a mini-review | Journal of Biological Engineering | Full Text

  https://jbioleng.biomedcentral.com/articles/10.1186/s13036-022-00291-y

  The AMD is a complex, chronic, multifactorial disease characterized by an aging macula in individuals with genetic mutations and environmental risk factors whose pathophysiology is poorly understood. It appears that genetic mutations, particularly in the complement genes, play an important role in establishing the disease. A large genome-wide association study identified 34 loci that clustered in three main pathways in AMD progression (in ascending order of p-value): the complement system, extracellular matrix remodeling, and lipoprotein metabolism. […] Aging causes choroidal thinning which is most likely due to a decreased choroidal vascular volume, secondary to the resultant decrease in choroidal blood perfusion. The severity of the choroidal perfusion deficits, particularly in the central macula, has been correlated with AMD severity and progression.

• #55 Dysfunctional autophagy in RPE, a contributing factor in age-related macular degeneration | Cell Death & Disease

  https://www.nature.com/articles/cddis2016453

  Autophagy is a lysosome-mediated degradation process for non-essential or damaged cellular constituents to supply the cell with energy and to maintain homeostasis. […] Recently, dysregulated autophagy in RPE was shown to increase susceptibility to oxidative stress and AMD. […] Here, we analyzed the phenotype and function of RPE cultures established from human donor eyes. […] our study suggests that impaired autophagy dynamics in RPE contributes to the pathophysiology of AMD. […] Analysis of autophagic efficiency showed dysfunctional autophagic activity and inability to induce autophagy in response to starvation in AMD RPE. […] Despite the observed accumulation of APs by EM, AMD RPE cultures failed to induce autophagy during starvation suggesting dysfunctional autophagy and significantly lower autophagic flux in AMD RPE. […] Together, these observations strongly suggest dysfunctional autophagy in AMD RPE that translates into lower autophagic flux and accumulation of cytoplasmic debris.

• #56 Dysfunctional autophagy in RPE, a contributing factor in age-related macular degeneration | Cell Death & Disease

  https://www.nature.com/articles/cddis2016453

  Autophagy is a lysosome-mediated degradation process for non-essential or damaged cellular constituents to supply the cell with energy and to maintain homeostasis. […] Recently, dysregulated autophagy in RPE was shown to increase susceptibility to oxidative stress and AMD. […] Here, we analyzed the phenotype and function of RPE cultures established from human donor eyes. […] our study suggests that impaired autophagy dynamics in RPE contributes to the pathophysiology of AMD. […] Analysis of autophagic efficiency showed dysfunctional autophagic activity and inability to induce autophagy in response to starvation in AMD RPE. […] Despite the observed accumulation of APs by EM, AMD RPE cultures failed to induce autophagy during starvation suggesting dysfunctional autophagy and significantly lower autophagic flux in AMD RPE. […] Together, these observations strongly suggest dysfunctional autophagy in AMD RPE that translates into lower autophagic flux and accumulation of cytoplasmic debris.

• #57 Dysfunctional autophagy in RPE, a contributing factor in age-related macular degeneration | Cell Death & Disease

  https://www.nature.com/articles/cddis2016453

  Autophagy is a lysosome-mediated degradation process for non-essential or damaged cellular constituents to supply the cell with energy and to maintain homeostasis. […] Recently, dysregulated autophagy in RPE was shown to increase susceptibility to oxidative stress and AMD. […] Here, we analyzed the phenotype and function of RPE cultures established from human donor eyes. […] our study suggests that impaired autophagy dynamics in RPE contributes to the pathophysiology of AMD. […] Analysis of autophagic efficiency showed dysfunctional autophagic activity and inability to induce autophagy in response to starvation in AMD RPE. […] Despite the observed accumulation of APs by EM, AMD RPE cultures failed to induce autophagy during starvation suggesting dysfunctional autophagy and significantly lower autophagic flux in AMD RPE. […] Together, these observations strongly suggest dysfunctional autophagy in AMD RPE that translates into lower autophagic flux and accumulation of cytoplasmic debris.

• #58 Dysfunctional autophagy in RPE, a contributing factor in age-related macular degeneration | Cell Death & Disease

  https://www.nature.com/articles/cddis2016453

  Autophagy is a lysosome-mediated degradation process for non-essential or damaged cellular constituents to supply the cell with energy and to maintain homeostasis. […] Recently, dysregulated autophagy in RPE was shown to increase susceptibility to oxidative stress and AMD. […] Here, we analyzed the phenotype and function of RPE cultures established from human donor eyes. […] our study suggests that impaired autophagy dynamics in RPE contributes to the pathophysiology of AMD. […] Analysis of autophagic efficiency showed dysfunctional autophagic activity and inability to induce autophagy in response to starvation in AMD RPE. […] Despite the observed accumulation of APs by EM, AMD RPE cultures failed to induce autophagy during starvation suggesting dysfunctional autophagy and significantly lower autophagic flux in AMD RPE. […] Together, these observations strongly suggest dysfunctional autophagy in AMD RPE that translates into lower autophagic flux and accumulation of cytoplasmic debris.

• #59 Age Related Macular Degeneration: a Complex Pathology

  https://austinpublishinggroup.com/genetics-genomic-research/fulltext/ajggr-v1-id1005.php

  An increased level of HTRA1 is suggested to play a potential role in the pathogenesis of AMD. […] In recent years, numerous clinical-genetic studies documented the crucial role of inflammation and immune-mediated processes (e.g. complement activation) in the pathogenesis of AMD. […] The hallmark of AMD, „drusen”, contains large amount of components involved in the complement pathway. […] The accumulation of macrophages in the AMD tissues suggest an important role for macrophages in AMD pathogenesis, which is well supported in AMD animal model studies. […] The precise roles and impacts of macrophages in AMD are unclear and debated in the AMD field. […] The autophagy processes are highly active in the RPE layer because RPE cells are subject to oxidative stress, high oxygen tension, lifelong light illumination, and are involve in daily phagocytosis of photoreceptor outer segments.

• #60 Age Related Macular Degeneration: a Complex Pathology

  https://austinpublishinggroup.com/genetics-genomic-research/fulltext/ajggr-v1-id1005.php

  The increased mitochondrial stress and dysfunctional autophagy in the RPE cells of AMD patients also support the involvement of autophagy in the pathology of AMD. […] To date, there is no consensus as to whether autophagy inhibitors or activators would be beneficial in AMD therapy. […] Despite several important findings in the last decade, we still do not have a clear picture of biological pathways that are actual culprits for AMD. […] These primary factors create a para-inflammatory environment which may provoke the infiltration of macrophages, lymphocytes, neutrophils and various cytokines to the degenerated tissue sites in AMD patients and cause further damage and lead to „wet AMD”.

• #61 Role of amyloid β-peptide in the pathogenesis of age-related macular degeneration | BMJ Open Ophthalmology

  https://bmjophth.bmj.com/content/6/1/e000774

  Age-related macular degeneration (AMD) is the most common eye disease in elderly patients, which could lead to irreversible vision loss and blindness. Increasing evidence indicates that amyloid -peptide (A) might be associated with the pathogenesis of AMD. […] A congregates in subretinal drusen of patients with AMD and participates in the pathogenesis of AMD through enhancing inflammatory activity, inducing mitochondrial dysfunction, altering ribosomal function, regulating the lysosomal pathway, affecting RNA splicing, modulating angiogenesis and modifying cell structure in AMD. […] A has been affirmed to be specifically prevalent in the extracellular soft drusen deposits of patients with AMD. […] Administration of A in the subretinal region of C57BL/6 mice has shown similar pathology with AMD which exacerbates the senescence of RPE cells and retinal degeneration, suggesting that A may be responsible for the characteristics of AMD.

• #62 Role of amyloid β-peptide in the pathogenesis of age-related macular degeneration | BMJ Open Ophthalmology

  https://bmjophth.bmj.com/content/6/1/e000774

  Age-related macular degeneration (AMD) is the most common eye disease in elderly patients, which could lead to irreversible vision loss and blindness. Increasing evidence indicates that amyloid -peptide (A) might be associated with the pathogenesis of AMD. […] A congregates in subretinal drusen of patients with AMD and participates in the pathogenesis of AMD through enhancing inflammatory activity, inducing mitochondrial dysfunction, altering ribosomal function, regulating the lysosomal pathway, affecting RNA splicing, modulating angiogenesis and modifying cell structure in AMD. […] A has been affirmed to be specifically prevalent in the extracellular soft drusen deposits of patients with AMD. […] Administration of A in the subretinal region of C57BL/6 mice has shown similar pathology with AMD which exacerbates the senescence of RPE cells and retinal degeneration, suggesting that A may be responsible for the characteristics of AMD.

• #63 Role of amyloid β-peptide in the pathogenesis of age-related macular degeneration | BMJ Open Ophthalmology

  https://bmjophth.bmj.com/content/6/1/e000774

  Age-related macular degeneration (AMD) is the most common eye disease in elderly patients, which could lead to irreversible vision loss and blindness. Increasing evidence indicates that amyloid -peptide (A) might be associated with the pathogenesis of AMD. […] A congregates in subretinal drusen of patients with AMD and participates in the pathogenesis of AMD through enhancing inflammatory activity, inducing mitochondrial dysfunction, altering ribosomal function, regulating the lysosomal pathway, affecting RNA splicing, modulating angiogenesis and modifying cell structure in AMD. […] A has been affirmed to be specifically prevalent in the extracellular soft drusen deposits of patients with AMD. […] Administration of A in the subretinal region of C57BL/6 mice has shown similar pathology with AMD which exacerbates the senescence of RPE cells and retinal degeneration, suggesting that A may be responsible for the characteristics of AMD.

• #64 Role of amyloid β-peptide in the pathogenesis of age-related macular degeneration | BMJ Open Ophthalmology

  https://bmjophth.bmj.com/content/6/1/e000774

  Age-related macular degeneration (AMD) is the most common eye disease in elderly patients, which could lead to irreversible vision loss and blindness. Increasing evidence indicates that amyloid -peptide (A) might be associated with the pathogenesis of AMD. […] A congregates in subretinal drusen of patients with AMD and participates in the pathogenesis of AMD through enhancing inflammatory activity, inducing mitochondrial dysfunction, altering ribosomal function, regulating the lysosomal pathway, affecting RNA splicing, modulating angiogenesis and modifying cell structure in AMD. […] A has been affirmed to be specifically prevalent in the extracellular soft drusen deposits of patients with AMD. […] Administration of A in the subretinal region of C57BL/6 mice has shown similar pathology with AMD which exacerbates the senescence of RPE cells and retinal degeneration, suggesting that A may be responsible for the characteristics of AMD.

• #65 Role of amyloid β-peptide in the pathogenesis of age-related macular degeneration | BMJ Open Ophthalmology

  https://bmjophth.bmj.com/content/6/1/e000774

  Several pathways involved in A enhancing the formation of AMD have been clarified in current researches. […] A-induced inflammatory activity, ribosomal dysfunction, oxidative phosphorylation dysregulation, spliceosome impairment, angiogenesis and cytoskeleton destabilisation cause numerous damages in the subretinal region, which is associated with the pathogenesis of AMD. […] Future research on the molecular mechanism of A-mediated pathogenesis of AMD may provide novel thoughts about potential therapies of AMD related to A.

• #66 Role of amyloid β-peptide in the pathogenesis of age-related macular degeneration | BMJ Open Ophthalmology

  https://bmjophth.bmj.com/content/6/1/e000774

  Several pathways involved in A enhancing the formation of AMD have been clarified in current researches. […] A-induced inflammatory activity, ribosomal dysfunction, oxidative phosphorylation dysregulation, spliceosome impairment, angiogenesis and cytoskeleton destabilisation cause numerous damages in the subretinal region, which is associated with the pathogenesis of AMD. […] Future research on the molecular mechanism of A-mediated pathogenesis of AMD may provide novel thoughts about potential therapies of AMD related to A.

• #67

  https://www.jci.org/articles/view/24635

  Drusen are extracellular deposits that lie beneath the retinal pigment epithelium (RPE) and are the earliest signs of age-related macular degeneration (AMD). […] Recent proteome analysis demonstrated that amyloid (A) deposition was specific to drusen from eyes with AMD. […] The present study demonstrates that A accumulation affects the balance between VEGF and PEDF in the RPE, and an accumulation of A reproduces features characteristic of human AMD, such as RPE atrophy and basal deposit formation. […] New evidence indicates that, in age-related macular degeneration (AMD), substructural elements within drusen contain A, which is a major component of senile plaques and cerebrovascular deposits in the brains of patients with AD. […] AMD is the leading cause of irreversible vision loss among the elderly in developed countries.

• #68

  https://www.jci.org/articles/view/24635

  It is believed that they may signal the presence of an altered pathophysiology of the RPE and, consequently, they may be a marker for the degree of diffuse RPE dysfunction in patients with AMD. […] However, it still remains unclear which component of drusen is a key contributor to the progression of AMD. […] In the present study, we hypothesized that A accumulated in drusen might induce the change of the expression of angiogenesis-related factors and cause cellular dysfunction in the RPE and therefore play a key role in the development of AMD. […] These results suggest that A may be a key contributor to the development of AMD. […] In senescent neprilysin-deficient mice, an animal model for AD, we showed A accumulation between RPE and the Bruch membrane in the eye as well as enhanced VEGF expression and diminished PEDF expression in the RPE layer, suggesting an imbalance between the expression of angiogenesis-related factors.

• #69 Age-Related Macular Degeneration (AMD): Pathophysiology, Drug Targeting Approaches, and Recent Developments in Nanotherapeutics

  https://www.mdpi.com/1648-9144/60/10/1647

  The RPE cells having genetic polymorphism in FH 402H demonstrate a high tendency of AMD via lowered mitochondrial and phagolysosome (L) activity. […] Lipids have a very crucial role in the pathogenesis of AMD i.e., in the form of drusen (lipid-containing deposits), the role of bioactive lipids as preventive therapy in AMD was explored by various groups. […] Studies have revealed that omega-3 polyunsaturated fatty acids (ω-3-PUFA) such as eicosapentaenoic acid from dietary sources such as fish and nuts reduced the risk of early AMD. […] It was observed that in hypoxic stimulation of neovascularization, the increasing ω-3-PUFA tissue levels led to vessel regrowth after injury leading to a decreased avascular zone of the retina in the case of AMD. […] The protective benefits of ω-3-PUFAs and their bioactive metabolites were mediated, in part, by the inhibition of tumor necrosis factor-α. […] The first major review that will cover various topics including etiology, Types and Symptoms, prevalence and risk factors; pathogenesis focusing on molecular aspects, particularly inflammatory, oxidative, and angiogenesis aspects; therapeutic intervention in AMD; strategic drug delivery approaches.

• #70 Age-Related Macular Degeneration (AMD): Pathophysiology, Drug Targeting Approaches, and Recent Developments in Nanotherapeutics

  https://www.mdpi.com/1648-9144/60/10/1647

  The RPE cells having genetic polymorphism in FH 402H demonstrate a high tendency of AMD via lowered mitochondrial and phagolysosome (L) activity. […] Lipids have a very crucial role in the pathogenesis of AMD i.e., in the form of drusen (lipid-containing deposits), the role of bioactive lipids as preventive therapy in AMD was explored by various groups. […] Studies have revealed that omega-3 polyunsaturated fatty acids (ω-3-PUFA) such as eicosapentaenoic acid from dietary sources such as fish and nuts reduced the risk of early AMD. […] It was observed that in hypoxic stimulation of neovascularization, the increasing ω-3-PUFA tissue levels led to vessel regrowth after injury leading to a decreased avascular zone of the retina in the case of AMD. […] The protective benefits of ω-3-PUFAs and their bioactive metabolites were mediated, in part, by the inhibition of tumor necrosis factor-α. […] The first major review that will cover various topics including etiology, Types and Symptoms, prevalence and risk factors; pathogenesis focusing on molecular aspects, particularly inflammatory, oxidative, and angiogenesis aspects; therapeutic intervention in AMD; strategic drug delivery approaches.

• #71 Age-Related Macular Degeneration (AMD): Pathophysiology, Drug Targeting Approaches, and Recent Developments in Nanotherapeutics

  https://www.mdpi.com/1648-9144/60/10/1647

  The RPE cells having genetic polymorphism in FH 402H demonstrate a high tendency of AMD via lowered mitochondrial and phagolysosome (L) activity. […] Lipids have a very crucial role in the pathogenesis of AMD i.e., in the form of drusen (lipid-containing deposits), the role of bioactive lipids as preventive therapy in AMD was explored by various groups. […] Studies have revealed that omega-3 polyunsaturated fatty acids (ω-3-PUFA) such as eicosapentaenoic acid from dietary sources such as fish and nuts reduced the risk of early AMD. […] It was observed that in hypoxic stimulation of neovascularization, the increasing ω-3-PUFA tissue levels led to vessel regrowth after injury leading to a decreased avascular zone of the retina in the case of AMD. […] The protective benefits of ω-3-PUFAs and their bioactive metabolites were mediated, in part, by the inhibition of tumor necrosis factor-α. […] The first major review that will cover various topics including etiology, Types and Symptoms, prevalence and risk factors; pathogenesis focusing on molecular aspects, particularly inflammatory, oxidative, and angiogenesis aspects; therapeutic intervention in AMD; strategic drug delivery approaches.

• #72 Age-Related Macular Degeneration (AMD): Pathophysiology, Drug Targeting Approaches, and Recent Developments in Nanotherapeutics

  https://www.mdpi.com/1648-9144/60/10/1647

  The RPE cells having genetic polymorphism in FH 402H demonstrate a high tendency of AMD via lowered mitochondrial and phagolysosome (L) activity. […] Lipids have a very crucial role in the pathogenesis of AMD i.e., in the form of drusen (lipid-containing deposits), the role of bioactive lipids as preventive therapy in AMD was explored by various groups. […] Studies have revealed that omega-3 polyunsaturated fatty acids (ω-3-PUFA) such as eicosapentaenoic acid from dietary sources such as fish and nuts reduced the risk of early AMD. […] It was observed that in hypoxic stimulation of neovascularization, the increasing ω-3-PUFA tissue levels led to vessel regrowth after injury leading to a decreased avascular zone of the retina in the case of AMD. […] The protective benefits of ω-3-PUFAs and their bioactive metabolites were mediated, in part, by the inhibition of tumor necrosis factor-α. […] The first major review that will cover various topics including etiology, Types and Symptoms, prevalence and risk factors; pathogenesis focusing on molecular aspects, particularly inflammatory, oxidative, and angiogenesis aspects; therapeutic intervention in AMD; strategic drug delivery approaches.

• #73 Macular degeneration – Wikipedia

  https://en.wikipedia.org/wiki/Macular_degeneration

  In the wet (exudative) form, which is more severe, blood vessels grow up from the choroid (neovascularization) behind the retina which can leak exudate and fluid and also cause hemorrhaging. […] Early work demonstrated a family of immune mediators was plentiful in drusen. […] Complement factor H (CFH) is an important inhibitor of this inflammatory cascade, and a disease-associated polymorphism in the CFH gene strongly associates with AMD. […] Thus an AMD pathophysiological model of chronic low grade complement activation and inflammation in the macula has been advanced. […] A powerful predictor of AMD is found on chromosome 10q26 at LOC 387715. […] Other gene markers of progression risk includes tissue inhibitor of metalloproteinase 3 (TIMP3), suggesting a role for extracellular matrix metabolism in AMD progression. […] The early stigmata of the disease, drusen, are rich in cholesterol, offering face validity to the results of genome-wide association studies.

• #74 Tissue engineering in age-related macular degeneration: a mini-review | Journal of Biological Engineering | Full Text

  https://jbioleng.biomedcentral.com/articles/10.1186/s13036-022-00291-y

  The AMD is a complex, chronic, multifactorial disease characterized by an aging macula in individuals with genetic mutations and environmental risk factors whose pathophysiology is poorly understood. It appears that genetic mutations, particularly in the complement genes, play an important role in establishing the disease. A large genome-wide association study identified 34 loci that clustered in three main pathways in AMD progression (in ascending order of p-value): the complement system, extracellular matrix remodeling, and lipoprotein metabolism. […] Aging causes choroidal thinning which is most likely due to a decreased choroidal vascular volume, secondary to the resultant decrease in choroidal blood perfusion. The severity of the choroidal perfusion deficits, particularly in the central macula, has been correlated with AMD severity and progression.

• #75 Tissue engineering in age-related macular degeneration: a mini-review | Journal of Biological Engineering | Full Text

  https://jbioleng.biomedcentral.com/articles/10.1186/s13036-022-00291-y

  These changes in choroidal hemodynamics appear to play a crucial role in the progression of intermediate AMD to late AMD. […] Hence, the BrM accumulates with lipids, especially lipoproteins that contain apolipoprotein B and E, cholesterol and 7-ketocholesterol. As a result, the aging macula experiences the deposition of lipid rich extracellular deposits known as drusen and subretinal drusenoid deposits (SDD), causing dry AMD. […] The lipoprotein deposited between the RPE and BrM (the subRPE space) is called Drusen, and the deposition between the RPE and the photoreceptors (the subretinal space) is called SDD. […] These deposits trigger the complement cascade, recruit the macrophage through the breaching BrM into sub RPE space, and activate the microglia in subretinal space, which further leads to local inflammatory responses. The complement system, a part of the innate immune system is unspecific, thus can lead to macular neovascularization (wet AMD) and macular atrophy. […] Patients with genetic polymorphisms of the complement genes are unable to turn off the complement cascade in the disease progression.

• #76 Tissue engineering in age-related macular degeneration: a mini-review | Journal of Biological Engineering | Full Text

  https://jbioleng.biomedcentral.com/articles/10.1186/s13036-022-00291-y

  These changes in choroidal hemodynamics appear to play a crucial role in the progression of intermediate AMD to late AMD. […] Hence, the BrM accumulates with lipids, especially lipoproteins that contain apolipoprotein B and E, cholesterol and 7-ketocholesterol. As a result, the aging macula experiences the deposition of lipid rich extracellular deposits known as drusen and subretinal drusenoid deposits (SDD), causing dry AMD. […] The lipoprotein deposited between the RPE and BrM (the subRPE space) is called Drusen, and the deposition between the RPE and the photoreceptors (the subretinal space) is called SDD. […] These deposits trigger the complement cascade, recruit the macrophage through the breaching BrM into sub RPE space, and activate the microglia in subretinal space, which further leads to local inflammatory responses. The complement system, a part of the innate immune system is unspecific, thus can lead to macular neovascularization (wet AMD) and macular atrophy. […] Patients with genetic polymorphisms of the complement genes are unable to turn off the complement cascade in the disease progression.

• #77 The Role of Inflammation in Age-Related Macular Degeneration

  https://www.ijbs.com/v16p2989.htm

  Current evidence indicated that inflammation plays an integral role in the entire pathogenesis of AMD, especially in CNV or GA. […] We summarize the mechanisms of inflammation-related cytokines and leukocytes, and look forward to getting more inspiration for clinical treatment in AMD. […] In aging eyes, due to the regulation of pro- and anti-inflammatory cytokines by RPE, low-grade chronic inflammation may be induced by these and continue for a long time, and then promote AMD pathogenesis. […] A variety of cytokines have been found to study the relationship between inflammation and the progression of AMD. […] Pro-inflammatory cytokines include IL-1, IL-2, IL-6, IL-8, IL-12, IL-17, TNF-, IFN-, colony-stimulating factor (CSF) -1. […] Evidence has been accumulated that IL-1 induced inflammasome increases the susceptibility of RPE cell to cytotoxicity mediated by photooxidative damage. […] In summary, a series of cytokines play constructive roles in the pathogenesis of AMD, including the formation of CNV and subretinal fibrosis. […] The development of novel targeted therapies could potentially be considered for further investigations.

• #78 The Role of Inflammation in Age-Related Macular Degeneration

  https://www.ijbs.com/v16p2989.htm

  Current evidence indicated that inflammation plays an integral role in the entire pathogenesis of AMD, especially in CNV or GA. […] We summarize the mechanisms of inflammation-related cytokines and leukocytes, and look forward to getting more inspiration for clinical treatment in AMD. […] In aging eyes, due to the regulation of pro- and anti-inflammatory cytokines by RPE, low-grade chronic inflammation may be induced by these and continue for a long time, and then promote AMD pathogenesis. […] A variety of cytokines have been found to study the relationship between inflammation and the progression of AMD. […] Pro-inflammatory cytokines include IL-1, IL-2, IL-6, IL-8, IL-12, IL-17, TNF-, IFN-, colony-stimulating factor (CSF) -1. […] Evidence has been accumulated that IL-1 induced inflammasome increases the susceptibility of RPE cell to cytotoxicity mediated by photooxidative damage. […] In summary, a series of cytokines play constructive roles in the pathogenesis of AMD, including the formation of CNV and subretinal fibrosis. […] The development of novel targeted therapies could potentially be considered for further investigations.

• #79 The Role of Inflammation in Age-Related Macular Degeneration

  https://www.ijbs.com/v16p2989.htm

  Current evidence indicated that inflammation plays an integral role in the entire pathogenesis of AMD, especially in CNV or GA. […] We summarize the mechanisms of inflammation-related cytokines and leukocytes, and look forward to getting more inspiration for clinical treatment in AMD. […] In aging eyes, due to the regulation of pro- and anti-inflammatory cytokines by RPE, low-grade chronic inflammation may be induced by these and continue for a long time, and then promote AMD pathogenesis. […] A variety of cytokines have been found to study the relationship between inflammation and the progression of AMD. […] Pro-inflammatory cytokines include IL-1, IL-2, IL-6, IL-8, IL-12, IL-17, TNF-, IFN-, colony-stimulating factor (CSF) -1. […] Evidence has been accumulated that IL-1 induced inflammasome increases the susceptibility of RPE cell to cytotoxicity mediated by photooxidative damage. […] In summary, a series of cytokines play constructive roles in the pathogenesis of AMD, including the formation of CNV and subretinal fibrosis. […] The development of novel targeted therapies could potentially be considered for further investigations.

• #80

  https://journals.lww.com/apjoo/fulltext/2023/03000/the_role_of_inflammation_in_age_related_macular.4.aspx

  Most of the current literature assessed the role of inflammation in the pathogenesis of wet AMD. […] Like dry AMD and GA, local inflammation is responsible of the degeneration of RPE and photoreceptors outer segment. […] Other than being a potent proinflammatory cytokine, IL-6 stimulates the signal transducer and activator of transcription-3 (STAT3), which has been associated with the development and growth of murine norovirus (MNV). […] The absence of this mediator was associated with gliotic degeneration of retinal glia driving the neuroinflammatory contribution to the onset and progression of MNV. […] The activation of the membrane attack complex (MAC) has been found involved in the angiogenetic process. […] Although the current scientific evidence agrees in considering inflammation as a major pathogenic component both of dry and wet AMD, several aspects remain unsolved. […] In conclusion, AMD shows a very intricate pathogenesis involving inflammation as a major cause of retinal damage and disease progression.

• #81

  https://journals.lww.com/apjoo/fulltext/2023/03000/the_role_of_inflammation_in_age_related_macular.4.aspx

  Most of the current literature assessed the role of inflammation in the pathogenesis of wet AMD. […] Like dry AMD and GA, local inflammation is responsible of the degeneration of RPE and photoreceptors outer segment. […] Other than being a potent proinflammatory cytokine, IL-6 stimulates the signal transducer and activator of transcription-3 (STAT3), which has been associated with the development and growth of murine norovirus (MNV). […] The absence of this mediator was associated with gliotic degeneration of retinal glia driving the neuroinflammatory contribution to the onset and progression of MNV. […] The activation of the membrane attack complex (MAC) has been found involved in the angiogenetic process. […] Although the current scientific evidence agrees in considering inflammation as a major pathogenic component both of dry and wet AMD, several aspects remain unsolved. […] In conclusion, AMD shows a very intricate pathogenesis involving inflammation as a major cause of retinal damage and disease progression.

• #82

  https://journals.lww.com/apjoo/fulltext/2023/03000/the_role_of_inflammation_in_age_related_macular.4.aspx

  Most of the current literature assessed the role of inflammation in the pathogenesis of wet AMD. […] Like dry AMD and GA, local inflammation is responsible of the degeneration of RPE and photoreceptors outer segment. […] Other than being a potent proinflammatory cytokine, IL-6 stimulates the signal transducer and activator of transcription-3 (STAT3), which has been associated with the development and growth of murine norovirus (MNV). […] The absence of this mediator was associated with gliotic degeneration of retinal glia driving the neuroinflammatory contribution to the onset and progression of MNV. […] The activation of the membrane attack complex (MAC) has been found involved in the angiogenetic process. […] Although the current scientific evidence agrees in considering inflammation as a major pathogenic component both of dry and wet AMD, several aspects remain unsolved. […] In conclusion, AMD shows a very intricate pathogenesis involving inflammation as a major cause of retinal damage and disease progression.

• #83 Microbiota and age-related macular degeneration: where are we today?

  https://journals.aboutscience.eu/index.php/aboutopen/article/download/2241/2319?inline=1

  Age-related macular degeneration (AMD) is a complex degenerative multifactorial retinal disease, representing a leading cause of legal blindness among elderly individuals. […] Recent studies support the existence of a gut-retina axis involved in the pathogenesis of several ocular diseases, including AMD. […] High-fat and high simple sugar diets determine a derangement of the gut microbiota, with an increase of gut permeability and systemic low-grade inflammation. […] Leaky gut is correlated with higher levels of circulating microbial-associated pattern molecules, which trigger the systemic release of potent proinflammatory mediators and stimulate the specific immune cells of the retina, contributing to retinal damage. […] All these findings suggest that microbiota is closely related to AMD and that it may be targeted in order to influence AMD pathogenesis and/or its clinical course.

• #84 Microbiota and age-related macular degeneration: where are we today?

  https://journals.aboutscience.eu/index.php/aboutopen/article/download/2241/2319?inline=1

  Age-related macular degeneration (AMD) is a complex degenerative multifactorial retinal disease, representing a leading cause of legal blindness among elderly individuals. […] Recent studies support the existence of a gut-retina axis involved in the pathogenesis of several ocular diseases, including AMD. […] High-fat and high simple sugar diets determine a derangement of the gut microbiota, with an increase of gut permeability and systemic low-grade inflammation. […] Leaky gut is correlated with higher levels of circulating microbial-associated pattern molecules, which trigger the systemic release of potent proinflammatory mediators and stimulate the specific immune cells of the retina, contributing to retinal damage. […] All these findings suggest that microbiota is closely related to AMD and that it may be targeted in order to influence AMD pathogenesis and/or its clinical course.

• #85 Microbiota and age-related macular degeneration: where are we today?

  https://journals.aboutscience.eu/index.php/aboutopen/article/download/2241/2319?inline=1

  Age-related macular degeneration (AMD) is a complex degenerative multifactorial retinal disease, representing a leading cause of legal blindness among elderly individuals. […] Recent studies support the existence of a gut-retina axis involved in the pathogenesis of several ocular diseases, including AMD. […] High-fat and high simple sugar diets determine a derangement of the gut microbiota, with an increase of gut permeability and systemic low-grade inflammation. […] Leaky gut is correlated with higher levels of circulating microbial-associated pattern molecules, which trigger the systemic release of potent proinflammatory mediators and stimulate the specific immune cells of the retina, contributing to retinal damage. […] All these findings suggest that microbiota is closely related to AMD and that it may be targeted in order to influence AMD pathogenesis and/or its clinical course.

• #86 Microbiota and age-related macular degeneration: where are we today?

  https://journals.aboutscience.eu/index.php/aboutopen/article/download/2241/2319?inline=1

  Age-related macular degeneration (AMD) is a complex degenerative multifactorial retinal disease, representing a leading cause of legal blindness among elderly individuals. […] Recent studies support the existence of a gut-retina axis involved in the pathogenesis of several ocular diseases, including AMD. […] High-fat and high simple sugar diets determine a derangement of the gut microbiota, with an increase of gut permeability and systemic low-grade inflammation. […] Leaky gut is correlated with higher levels of circulating microbial-associated pattern molecules, which trigger the systemic release of potent proinflammatory mediators and stimulate the specific immune cells of the retina, contributing to retinal damage. […] All these findings suggest that microbiota is closely related to AMD and that it may be targeted in order to influence AMD pathogenesis and/or its clinical course.

• #87 Microbiota and age-related macular degeneration: where are we today?

  https://journals.aboutscience.eu/index.php/aboutopen/article/download/2241/2319?inline=1

  There is a common denominator that connects aging, diet, and obesity, and this is the gut microbiota. Recent studies indicate a role for gut microbiota in the development of AMD in mouse models and in some forms of human AMD. […] Alterations in the composition of the gut microbiota, also termed dysbiosis, markedly affect the intestinal epithelial barrier and challenge the host immune system. […] Gut microbiota influence the pathogenesis of many diseases, as it can determine an increasing of the intestinal permeability (leaky gut), which allows the translocation of bacterial products and toxic substances in the blood. […] Thus, bacterial products such as the endotoxin lipopolysaccharides (LPS) and pathogen-associated molecular pattern molecules (PAMPs) are translocated into the blood flow, inducing low-grade inflammation in several tissues through the activation of pattern recognition receptors (PRRs); in addition, the metabolites produced by gut microbiota can stimulate the specific immune cells of the retina.

• #88 Microbiota and age-related macular degeneration: where are we today?

  https://journals.aboutscience.eu/index.php/aboutopen/article/download/2241/2319?inline=1

  There is a common denominator that connects aging, diet, and obesity, and this is the gut microbiota. Recent studies indicate a role for gut microbiota in the development of AMD in mouse models and in some forms of human AMD. […] Alterations in the composition of the gut microbiota, also termed dysbiosis, markedly affect the intestinal epithelial barrier and challenge the host immune system. […] Gut microbiota influence the pathogenesis of many diseases, as it can determine an increasing of the intestinal permeability (leaky gut), which allows the translocation of bacterial products and toxic substances in the blood. […] Thus, bacterial products such as the endotoxin lipopolysaccharides (LPS) and pathogen-associated molecular pattern molecules (PAMPs) are translocated into the blood flow, inducing low-grade inflammation in several tissues through the activation of pattern recognition receptors (PRRs); in addition, the metabolites produced by gut microbiota can stimulate the specific immune cells of the retina.

• #89 Pathway activation profiling reveals new insights into Age-related Macular Degeneration and provides avenues for therapeutic interventions | Aging

  http://www.aging-us.com/article/100711/text

  To conclude, AMD originates from at least 3 groups of signaling pathways: lipid metabolism (in the preclinical stage) dysregulation of these pathways leads to accumulation of insoluble deposits; complement pathways (preclinical and clinical stage) aberrant activation of these pathways leads to drusen formation, their extension and subsequent photoreceptor degeneration; and angiogenesis pathways (clinical stage) abnormal activation of these pathways leads to neovascularization, and new blood vessel outgrowth into the RPE area. […] Taking together already established facts and our new findings, we demonstrated that AMD is a single origin disease with multiple phenotypes, and which has an aging related lipid metabolism dysregulation as a starting point, followed by simultaneous aberrant activation of immune and inflammatory signaling pathways leading to a state of chronic local inflammation, followed by degeneration and neovascularization of affected tissues.

• #90 Pathway activation profiling reveals new insights into Age-related Macular Degeneration and provides avenues for therapeutic interventions | Aging

  http://www.aging-us.com/article/100711/text

  To conclude, AMD originates from at least 3 groups of signaling pathways: lipid metabolism (in the preclinical stage) dysregulation of these pathways leads to accumulation of insoluble deposits; complement pathways (preclinical and clinical stage) aberrant activation of these pathways leads to drusen formation, their extension and subsequent photoreceptor degeneration; and angiogenesis pathways (clinical stage) abnormal activation of these pathways leads to neovascularization, and new blood vessel outgrowth into the RPE area. […] Taking together already established facts and our new findings, we demonstrated that AMD is a single origin disease with multiple phenotypes, and which has an aging related lipid metabolism dysregulation as a starting point, followed by simultaneous aberrant activation of immune and inflammatory signaling pathways leading to a state of chronic local inflammation, followed by degeneration and neovascularization of affected tissues.

• #91 Pathway activation profiling reveals new insights into Age-related Macular Degeneration and provides avenues for therapeutic interventions | Aging

  http://www.aging-us.com/article/100711/text

  To conclude, AMD originates from at least 3 groups of signaling pathways: lipid metabolism (in the preclinical stage) dysregulation of these pathways leads to accumulation of insoluble deposits; complement pathways (preclinical and clinical stage) aberrant activation of these pathways leads to drusen formation, their extension and subsequent photoreceptor degeneration; and angiogenesis pathways (clinical stage) abnormal activation of these pathways leads to neovascularization, and new blood vessel outgrowth into the RPE area. […] Taking together already established facts and our new findings, we demonstrated that AMD is a single origin disease with multiple phenotypes, and which has an aging related lipid metabolism dysregulation as a starting point, followed by simultaneous aberrant activation of immune and inflammatory signaling pathways leading to a state of chronic local inflammation, followed by degeneration and neovascularization of affected tissues.

• #92 Pathway activation profiling reveals new insights into Age-related Macular Degeneration and provides avenues for therapeutic interventions | Aging

  http://www.aging-us.com/article/100711/text

  To conclude, AMD originates from at least 3 groups of signaling pathways: lipid metabolism (in the preclinical stage) dysregulation of these pathways leads to accumulation of insoluble deposits; complement pathways (preclinical and clinical stage) aberrant activation of these pathways leads to drusen formation, their extension and subsequent photoreceptor degeneration; and angiogenesis pathways (clinical stage) abnormal activation of these pathways leads to neovascularization, and new blood vessel outgrowth into the RPE area. […] Taking together already established facts and our new findings, we demonstrated that AMD is a single origin disease with multiple phenotypes, and which has an aging related lipid metabolism dysregulation as a starting point, followed by simultaneous aberrant activation of immune and inflammatory signaling pathways leading to a state of chronic local inflammation, followed by degeneration and neovascularization of affected tissues.

• #93 Pathway activation profiling reveals new insights into Age-related Macular Degeneration and provides avenues for therapeutic interventions | Aging

  http://www.aging-us.com/article/100711/text

  To conclude, AMD originates from at least 3 groups of signaling pathways: lipid metabolism (in the preclinical stage) dysregulation of these pathways leads to accumulation of insoluble deposits; complement pathways (preclinical and clinical stage) aberrant activation of these pathways leads to drusen formation, their extension and subsequent photoreceptor degeneration; and angiogenesis pathways (clinical stage) abnormal activation of these pathways leads to neovascularization, and new blood vessel outgrowth into the RPE area. […] Taking together already established facts and our new findings, we demonstrated that AMD is a single origin disease with multiple phenotypes, and which has an aging related lipid metabolism dysregulation as a starting point, followed by simultaneous aberrant activation of immune and inflammatory signaling pathways leading to a state of chronic local inflammation, followed by degeneration and neovascularization of affected tissues.

• #94 Pathogenic Mechanisms

  https://amdbook.org/book/export/html/21

  With all of the above in mind, Zarbin has summarized his review on AMD pathogenesis in five sequential steps as follows: (1) AMD involves aging changes plus additional pathological changes (ie, AMD is not just an aging change); (2) in aging and AMD, oxidative stress causes RPE and, possibly, choriocapillaris injury; (3) in AMD (and perhaps in aging), RPE and, possibly, choriocapillaris injury results in a chronic inflammatory response within the Bruch membrane and the choroid; (4) in AMD, RPE and, possibly, choriocapillaris injury and inflammation lead to formation of an abnormal extracellular matrix, which causes altered diffusion of nutrients to the retina and RPE, possibly precipitating further RPE and retinal damage; and (5) the abnormal extracellular matrix results in altered RPE-choriocapillaris behavior leading ultimately to atrophy of the retina, RPE, and choriocapillaris and/or choroidal new vessel growth. In this sequence of events, patient’s susceptibility to AMD would be determined by both the environment and his genetic profile.

• #95 Pathogenic Mechanisms

  https://amdbook.org/book/export/html/21

  With all of the above in mind, Zarbin has summarized his review on AMD pathogenesis in five sequential steps as follows: (1) AMD involves aging changes plus additional pathological changes (ie, AMD is not just an aging change); (2) in aging and AMD, oxidative stress causes RPE and, possibly, choriocapillaris injury; (3) in AMD (and perhaps in aging), RPE and, possibly, choriocapillaris injury results in a chronic inflammatory response within the Bruch membrane and the choroid; (4) in AMD, RPE and, possibly, choriocapillaris injury and inflammation lead to formation of an abnormal extracellular matrix, which causes altered diffusion of nutrients to the retina and RPE, possibly precipitating further RPE and retinal damage; and (5) the abnormal extracellular matrix results in altered RPE-choriocapillaris behavior leading ultimately to atrophy of the retina, RPE, and choriocapillaris and/or choroidal new vessel growth. In this sequence of events, patient’s susceptibility to AMD would be determined by both the environment and his genetic profile.

• #96 Age-Related Macular Degeneration (AMD or ARMD) – Eye Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/eye-disorders/retinal-disorders/age-related-macular-degeneration-amd-or-armd

  The choice of other treatments depends on the size, location, and type of neovascularization. […] Intravitreal injection of antivascular endothelial growth factor (anti-VEGF) medications (usually ranibizumab, bevacizumab, or aflibercept) can substantially reduce the risk of vision loss and can preserve useful vision in 20% of patients over their lifetime and reading vision in up to one-third of patients. […] Newer intravitreal medications are now available that provide extended duration of treatment; these include faricimab as well as high-dose aflibercept. […] Faricimab functions as a dual-mechanism medication binding VEGF-A and angiopoietin-2; efficacy is similar to that of aflibercept. […] In 2021, an implantable port delivery system for ranibizumab became available for the treatment of wet AMD. […] In 2020, intravitreal brolucizumab became available for the treatment of wet AMD; however, early reports suggest a higher incidence of adverse events with this medication than with other intravitreal anti-VEGF injections, including intraocular inflammation, retinal artery occlusion, and vasculitis.

• #97 Age-Related Macular Degeneration (AMD or ARMD) – Eye Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/eye-disorders/retinal-disorders/age-related-macular-degeneration-amd-or-armd

  The choice of other treatments depends on the size, location, and type of neovascularization. […] Intravitreal injection of antivascular endothelial growth factor (anti-VEGF) medications (usually ranibizumab, bevacizumab, or aflibercept) can substantially reduce the risk of vision loss and can preserve useful vision in 20% of patients over their lifetime and reading vision in up to one-third of patients. […] Newer intravitreal medications are now available that provide extended duration of treatment; these include faricimab as well as high-dose aflibercept. […] Faricimab functions as a dual-mechanism medication binding VEGF-A and angiopoietin-2; efficacy is similar to that of aflibercept. […] In 2021, an implantable port delivery system for ranibizumab became available for the treatment of wet AMD. […] In 2020, intravitreal brolucizumab became available for the treatment of wet AMD; however, early reports suggest a higher incidence of adverse events with this medication than with other intravitreal anti-VEGF injections, including intraocular inflammation, retinal artery occlusion, and vasculitis.

• #98 Age-Related Macular Degeneration (AMD or ARMD) – Eye Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/eye-disorders/retinal-disorders/age-related-macular-degeneration-amd-or-armd

  The choice of other treatments depends on the size, location, and type of neovascularization. […] Intravitreal injection of antivascular endothelial growth factor (anti-VEGF) medications (usually ranibizumab, bevacizumab, or aflibercept) can substantially reduce the risk of vision loss and can preserve useful vision in 20% of patients over their lifetime and reading vision in up to one-third of patients. […] Newer intravitreal medications are now available that provide extended duration of treatment; these include faricimab as well as high-dose aflibercept. […] Faricimab functions as a dual-mechanism medication binding VEGF-A and angiopoietin-2; efficacy is similar to that of aflibercept. […] In 2021, an implantable port delivery system for ranibizumab became available for the treatment of wet AMD. […] In 2020, intravitreal brolucizumab became available for the treatment of wet AMD; however, early reports suggest a higher incidence of adverse events with this medication than with other intravitreal anti-VEGF injections, including intraocular inflammation, retinal artery occlusion, and vasculitis.

• #99 Age-Related Macular Degeneration (AMD or ARMD) – Eye Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/eye-disorders/retinal-disorders/age-related-macular-degeneration-amd-or-armd

  The choice of other treatments depends on the size, location, and type of neovascularization. […] Intravitreal injection of antivascular endothelial growth factor (anti-VEGF) medications (usually ranibizumab, bevacizumab, or aflibercept) can substantially reduce the risk of vision loss and can preserve useful vision in 20% of patients over their lifetime and reading vision in up to one-third of patients. […] Newer intravitreal medications are now available that provide extended duration of treatment; these include faricimab as well as high-dose aflibercept. […] Faricimab functions as a dual-mechanism medication binding VEGF-A and angiopoietin-2; efficacy is similar to that of aflibercept. […] In 2021, an implantable port delivery system for ranibizumab became available for the treatment of wet AMD. […] In 2020, intravitreal brolucizumab became available for the treatment of wet AMD; however, early reports suggest a higher incidence of adverse events with this medication than with other intravitreal anti-VEGF injections, including intraocular inflammation, retinal artery occlusion, and vasculitis.

• #100 Age-Related Macular Degeneration (AMD or ARMD) – Eye Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/eye-disorders/retinal-disorders/age-related-macular-degeneration-amd-or-armd

  The choice of other treatments depends on the size, location, and type of neovascularization. […] Intravitreal injection of antivascular endothelial growth factor (anti-VEGF) medications (usually ranibizumab, bevacizumab, or aflibercept) can substantially reduce the risk of vision loss and can preserve useful vision in 20% of patients over their lifetime and reading vision in up to one-third of patients. […] Newer intravitreal medications are now available that provide extended duration of treatment; these include faricimab as well as high-dose aflibercept. […] Faricimab functions as a dual-mechanism medication binding VEGF-A and angiopoietin-2; efficacy is similar to that of aflibercept. […] In 2021, an implantable port delivery system for ranibizumab became available for the treatment of wet AMD. […] In 2020, intravitreal brolucizumab became available for the treatment of wet AMD; however, early reports suggest a higher incidence of adverse events with this medication than with other intravitreal anti-VEGF injections, including intraocular inflammation, retinal artery occlusion, and vasculitis.

• #101 Age-Related Macular Degeneration (AMD or ARMD) – Eye Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/eye-disorders/retinal-disorders/age-related-macular-degeneration-amd-or-armd

  Wet AMD occurs when new abnormal blood vessels develop under the retina in a process called choroidal neovascularization (abnormal new vessel formation). […] Localized macular edema or hemorrhage may elevate an area of the macula or cause a localized retinal pigment epithelial detachment. […] Eventually, untreated neovascularization causes a disciform scar under the macula. […] In general, the management of dry AMD focuses on nutritional supplementation to slow disease progression, whereas wet AMD is also treated with intravitreal anti-VEGF or laser therapy. […] In 2023, intravitreal pegcetacoplan and intravitreal avacincaptad pegol became available for the treatment of advanced dry AMD due to geographic atrophy. […] These medications inhibit the complement pathway and can slow the progression of geographic atrophy.

• #102 Age-Related Macular Degeneration (AMD or ARMD) – Eye Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/eye-disorders/retinal-disorders/age-related-macular-degeneration-amd-or-armd

  Wet AMD occurs when new abnormal blood vessels develop under the retina in a process called choroidal neovascularization (abnormal new vessel formation). […] Localized macular edema or hemorrhage may elevate an area of the macula or cause a localized retinal pigment epithelial detachment. […] Eventually, untreated neovascularization causes a disciform scar under the macula. […] In general, the management of dry AMD focuses on nutritional supplementation to slow disease progression, whereas wet AMD is also treated with intravitreal anti-VEGF or laser therapy. […] In 2023, intravitreal pegcetacoplan and intravitreal avacincaptad pegol became available for the treatment of advanced dry AMD due to geographic atrophy. […] These medications inhibit the complement pathway and can slow the progression of geographic atrophy.

• #103 Role of Mitochondrial Dysfunction in Dry Age-Related Macular Degeneration – Retina Today

  https://retinatoday.com/articles/2015-may-june/role-of-mitochondrial-dysfunction-in-dry-age-related-macular-degeneration

  Mitochondrial dysfunction induced by environmental toxicants may be an important risk factor in the etiology of dry age-related macular degeneration (AMD). […] The pathogenesis of dry AMD is multifactorial, and it includes aging, genetic abnormalities, systemic health, environmental risk factors (including cigarette smoking), and mitochondrial dysfunction. […] Mitochondrial dysfunction has been implicated in the etiology of dry AMD. […] Mitochondrial dysmorphology observed in RPE in eyes with AMD is consistent with severe dysfunction, and mitochondrial DNA from these eyes demonstrate increased oxidative damage. […] A novel mitochondrial protective compound, MTP-131, is a topical ophthalmologic investigational drug under development to treat both common and rare eye disorders, including retinal diseases and inherited mitochondrial optic neuropathies.

• #104 Role of Mitochondrial Dysfunction in Dry Age-Related Macular Degeneration – Retina Today

  https://retinatoday.com/articles/2015-may-june/role-of-mitochondrial-dysfunction-in-dry-age-related-macular-degeneration

  Our research has shown that RPE mitochondria are a major target of HQ in the eye, and that HQ exposure induces acute and chronic mitochondrial dysfunction resulting in biochemical and cellular changes consistent with dry AMD. […] MTP-131 prevented HQ-induced mitochondrial dysfunction, activation of biochemical injury pathways, and cellular functions associated with deposits.

• #105 Mitochondrial Repair in Dry Age-Related Macular Degeneration | Retinal Physician

  https://www.retinalphysician.com/issues/2019/april/mitochondrial-repair-in-dry-age-related-macular-degeneration/

  RPE cell damage is considered the hallmark of dry AMD. […] Finding potential effective modalities that decrease mitochondrial damage could lead to a treatment regimen for dry AMD. […] Some researchers believe that mitochondria can self-repair to conserve mtDNA architecture. […] Reduced levels of the DNA repair enzyme 8-oxoG DNA glycosylase1 (OGG1) were observed in RPE cells from aged donors or AMD patients, causing RPE loss and atrophy. […] Targeting mitochondria with human OGG1 could be a novel therapy that would boost mtDNA repair efficiency and protect against apoptosis that leads to RPE atrophy. […] Mitochondrial-derived peptides (MDPs) have neuroprotection, cytoprotection, anti-oxidant, and anti-inflammatory properties. […] Other damaged regions in AMD involve mtDNA genes for multiple subunits of complex I and complex III.

• #106 Aging-US | A Novel Discovery in Age-Related Macular Degeneration (AMD) | Aging

  https://www.aging-us.com/news_room/novel-discovery-in-age-related-macular-degeneration

  Inflammatory processes drive the progression of age-related macular degeneration (AMD) diseasea leading cause of vision loss in the United States. […] Humanin G (HNG) is a mitochondrial derived peptide that is cytoprotective in AMD and can protect against mitochondrial and cellular stress induced by damaged AMD mitochondria. […] The goal of this study was to test our hypothesis that inflammation-associated marker protein levels are increased in AMD and treatment with HNG leads to reduction in their protein levels. […] Humanin G was added to AMD and normal (control) cybrids derived from clinically characterized AMD patients and normal (control) subjects. […] Compared to control plasma samples, AMD plasma showed higher protein levels of inflammation markers. […] However, plasma levels of endogenous Humanin protein were 36.58% lower in AMD patients compared to that in age-matched normal subjects.

• #107 Mitochondrial Repair in Dry Age-Related Macular Degeneration | Retinal Physician

  https://www.retinalphysician.com/issues/2019/april/mitochondrial-repair-in-dry-age-related-macular-degeneration/

  The risk allele for complement factor H, regulator of the alternative complement pathway, increases the risk of mtDNA damage. […] Antioxidant agents, such as alpha-lipoic acid, alpha-tocopherol, genistein, resveratrol, memantine, MitoQ, and Mito-CP, may preserve mitochondrial function by decelerating the progression to blindness in AMD patients. […] Mitochondria-targeting drugs present great potential for future interventions in patients with dry AMD.

• #108 Novel treatments and genetics of age-related macular degeneration-a narrative review – Arabi – Annals of Eye Science

  https://aes.amegroups.org/article/view/6375/html

  Theoretically, intravitreal HMR 59 (AAVCAGsCD59) may provide a therapeutic opportunity for dry AMD, since it can affect the pathogenesis of the disease through inhibiting the complement cascade. […] Gene therapy has attracted the attention of researchers in the field of ocular diseases. […] AMD is a complex disease, and several genetic variants and environmental factors contribute to the pathogenesis of disease.

• #109 Alkeus Pharmaceuticals Presents Gildeuretinol Data During the Association for Research in Vision and Ophthalmology (ARVO) 2025 Annual Meeting May 4-8, 2025 – BioSpace

  https://www.biospace.com/press-releases/alkeus-pharmaceuticals-presents-gildeuretinol-data-during-the-association-for-research-in-vision-and-ophthalmology-arvo-2025-annual-meeting-may-4-8-2025

  GA secondary to AMD and Stargardt disease share a common pathophysiology, the accumulation of vitamin A dimers that are toxic to the retina. […] Gildeuretinol is currently being evaluated in clinical trials for the treatment of Stargardt disease and for geographic atrophy secondary to age-related macular degeneration. […] The Study of ALK-001 in GA secondary to age-related macular degeneration (SAGA) was a 24-month, double-masked, randomized, placebo-controlled trial to investigate safety, pharmacokinetics, tolerability and efficacy in 198 patients with geographic atrophy secondary to age-related macular degeneration and is complete.

• #110 Alkeus Pharmaceuticals Presents Gildeuretinol Data During

  https://www.globenewswire.com/news-release/2025/05/07/3076162/0/en/Alkeus-Pharmaceuticals-Presents-Gildeuretinol-Data-During-the-Association-for-Research-in-Vision-and-Ophthalmology-ARVO-2025-Annual-Meeting-May-4-8-2025.html

  Participants treated with gildeuretinol in the SAGA study in geographic atrophy (GA) secondary to age-related macular degeneration (AMD) showed a slower decline in vision-related quality of life and functional reading scores compared to placebo, demonstrating functional benefit […] GA secondary to AMD and Stargardt disease share a common pathophysiology, the accumulation of vitamin A dimers that are toxic to the retina. […] Gildeuretinol also demonstrated a statistically significant visual function improvement, showing 4.4 fewer letters lost (p=0.031) in low luminance visual acuity (LLVA) over 24 months, the first key secondary endpoint. […] These results demonstrate that gildeuretinol should be further evaluated as a potential systemic treatment of GA secondary to AMD. […] Oral gildeuretinol acetate (ALK-001) is a new molecular entity designed to reduce the dimerization of vitamin A without modulating the visual cycle. Gildeuretinol is currently being evaluated in clinical trials for the treatment of Stargardt disease and for geographic atrophy secondary to age-related macular degeneration.

• #111 Galimedix Therapeutics completes single ascending dose portion of phase 1 trial assessing GAL-101

  https://www.ophthalmologytimes.com/view/galimedix-therapeutics-completes-single-ascending-dose-portion-of-phase-1-trial-assessing-gal-101

  GAL-101 targets misfolded amyloid beta monomers to prevent toxic oligomer and protofibril formation, crucial in neurodegenerative diseases. […] GAL-101 demonstrated neuroprotective potential and symptomatic alleviation in preclinical Alzheimers models, with ongoing phase 2 trials for dry AMD. […] In targeting misfolded A monomers, GAL-101 works to prevent the formation of toxic A oligomers and protofibrils. Many studies have indicated that these A aggregates are a major underlying cause of neurodegenerative diseases of the eye, and recent approvals of anti-A drugs have also validated them as a key target in Alzheimers disease, the release stated. […] GAL-101s efficacy in protecting neuronal retinal cells from toxic damage has otherwise been demonstrated in other relevant ophthalmic preclinical models.

• #112 Nonexudative (Dry) Age-Related Macular Degeneration (AMD): Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1223154-overview

  Antioxidant multivitamin therapy (consisting of vitamin A at 25,000 IU, vitamin C at 500 mg, zinc at 80 mg, copper at 2 mg, and vitamin E at 400 mg) has been shown in a large clinical trial, the Age-Related Eye Diseases Study (AREDS), to be helpful in decreasing the risk of visual loss with nonexudative AMD. […] Current molecules under investigation aim to inhibit GA progression via various mechanisms, including reducing toxic byproduct generation and accumulation, slowing the visual cycle, and inhibiting the complement pathway, which have all been shown to be involved in the pathogenesis of AMD. Targeting the alternate complement pathway has shown the most promise for dry AMD treatment. More specifically, complement factor H mutations have been linked to dry AMD, and smoking, a known risk factor for AMD progression, alters activity of complement factor H.

• #113 A systems biology approach towards understanding and treating non-neovascular age-related macular degeneration | Nature Communications

  https://www.nature.com/articles/s41467-019-11262-1

  Photoreceptor cell death is the basis for permanent visual decline in dry AMD. […] The mechanisms for RPE cell death may differ from those of photoreceptors. […] The association of APOE variants with AMD was the first indication that a specific gene affected disease risk. […] Current research has focused on understanding the role of specific genes and related pathways that drive AMD pathobiology. […] The emergence of single-cell RNA and ATAC sequencing offers the possibility of defining the relative contributions of individual cell types to AMD pathogenesis, and will enrich the models that are developed. […] Future directions in dry AMD research should emphasize systems biology approaches that integrate omic, pharmacological, and clinical data into mathematical models that can predict disease onset and progression, identify biomarkers, establish disease causing mechanisms, and monitor response to therapy.

• #114 A systems biology approach towards understanding and treating non-neovascular age-related macular degeneration | Nature Communications

  https://www.nature.com/articles/s41467-019-11262-1

  Photoreceptor cell death is the basis for permanent visual decline in dry AMD. […] The mechanisms for RPE cell death may differ from those of photoreceptors. […] The association of APOE variants with AMD was the first indication that a specific gene affected disease risk. […] Current research has focused on understanding the role of specific genes and related pathways that drive AMD pathobiology. […] The emergence of single-cell RNA and ATAC sequencing offers the possibility of defining the relative contributions of individual cell types to AMD pathogenesis, and will enrich the models that are developed. […] Future directions in dry AMD research should emphasize systems biology approaches that integrate omic, pharmacological, and clinical data into mathematical models that can predict disease onset and progression, identify biomarkers, establish disease causing mechanisms, and monitor response to therapy.

• #115 Age Related Macular Degeneration: a Complex Pathology

  https://austinpublishinggroup.com/genetics-genomic-research/fulltext/ajggr-v1-id1005.php

  An increased level of HTRA1 is suggested to play a potential role in the pathogenesis of AMD. […] In recent years, numerous clinical-genetic studies documented the crucial role of inflammation and immune-mediated processes (e.g. complement activation) in the pathogenesis of AMD. […] The hallmark of AMD, „drusen”, contains large amount of components involved in the complement pathway. […] The accumulation of macrophages in the AMD tissues suggest an important role for macrophages in AMD pathogenesis, which is well supported in AMD animal model studies. […] The precise roles and impacts of macrophages in AMD are unclear and debated in the AMD field. […] The autophagy processes are highly active in the RPE layer because RPE cells are subject to oxidative stress, high oxygen tension, lifelong light illumination, and are involve in daily phagocytosis of photoreceptor outer segments.

• #116 Age Related Macular Degeneration: a Complex Pathology

  https://austinpublishinggroup.com/genetics-genomic-research/fulltext/ajggr-v1-id1005.php

  The increased mitochondrial stress and dysfunctional autophagy in the RPE cells of AMD patients also support the involvement of autophagy in the pathology of AMD. […] To date, there is no consensus as to whether autophagy inhibitors or activators would be beneficial in AMD therapy. […] Despite several important findings in the last decade, we still do not have a clear picture of biological pathways that are actual culprits for AMD. […] These primary factors create a para-inflammatory environment which may provoke the infiltration of macrophages, lymphocytes, neutrophils and various cytokines to the degenerated tissue sites in AMD patients and cause further damage and lead to „wet AMD”.

• #117 Role of amyloid β-peptide in the pathogenesis of age-related macular degeneration | BMJ Open Ophthalmology

  https://bmjophth.bmj.com/content/6/1/e000774

  Several pathways involved in A enhancing the formation of AMD have been clarified in current researches. […] A-induced inflammatory activity, ribosomal dysfunction, oxidative phosphorylation dysregulation, spliceosome impairment, angiogenesis and cytoskeleton destabilisation cause numerous damages in the subretinal region, which is associated with the pathogenesis of AMD. […] Future research on the molecular mechanism of A-mediated pathogenesis of AMD may provide novel thoughts about potential therapies of AMD related to A.

• #118 Systems-level analysis of age-related macular degeneration reveals global biomarkers and phenotype-specific functional networks | Genome Medicine | Full Text

  https://genomemedicine.biomedcentral.com/articles/10.1186/gm315

  Our findings reveal that cell-based inflammatory responses within the RPE-choroid are a core feature of AMD. […] Determining the cellular source(s), context-specific cellular target(s), and regulatory mechanism(s) of AMD-associated chemokines remains an important goal of future work. […] In summary, these data support the model that aging, environmental stressors, and genetic predisposition all hasten the onset and progression of cell-based immunological events, leading to a state of chronic local inflammation that mediates the development of the neovascular and/or atrophic changes characteristic of advanced AMD.

• #119 Microbiota and age-related macular degeneration: where are we today?

  https://journals.aboutscience.eu/index.php/aboutopen/article/download/2241/2319?inline=1

  All this evidence supports the existence of a gut-retina axis involved in the pathogenesis of ocular diseases, mainly AMD. […] Several studies support the evidence that high-fat and high simple sugar diets determine a derangement of the gut microbiota that leads to an increase of intestinal wall permeability and systemic low-grade inflammation. […] As a consequence, the metabolites produced by gut microbiota stimulate the specific immune cells of the retina, contributing to retinal damage. […] In conclusion, nutritional habits and micronutrient intake are able to influence AMD pathogenesis and/or its clinical course.

• #120 Age Related Macular Degeneration: a Complex Pathology

  https://austinpublishinggroup.com/genetics-genomic-research/fulltext/ajggr-v1-id1005.php

  The increased mitochondrial stress and dysfunctional autophagy in the RPE cells of AMD patients also support the involvement of autophagy in the pathology of AMD. […] To date, there is no consensus as to whether autophagy inhibitors or activators would be beneficial in AMD therapy. […] Despite several important findings in the last decade, we still do not have a clear picture of biological pathways that are actual culprits for AMD. […] These primary factors create a para-inflammatory environment which may provoke the infiltration of macrophages, lymphocytes, neutrophils and various cytokines to the degenerated tissue sites in AMD patients and cause further damage and lead to „wet AMD”.

• #121

  https://journals.lww.com/apjoo/fulltext/2023/03000/the_role_of_inflammation_in_age_related_macular.4.aspx

  Most of the current literature assessed the role of inflammation in the pathogenesis of wet AMD. […] Like dry AMD and GA, local inflammation is responsible of the degeneration of RPE and photoreceptors outer segment. […] Other than being a potent proinflammatory cytokine, IL-6 stimulates the signal transducer and activator of transcription-3 (STAT3), which has been associated with the development and growth of murine norovirus (MNV). […] The absence of this mediator was associated with gliotic degeneration of retinal glia driving the neuroinflammatory contribution to the onset and progression of MNV. […] The activation of the membrane attack complex (MAC) has been found involved in the angiogenetic process. […] Although the current scientific evidence agrees in considering inflammation as a major pathogenic component both of dry and wet AMD, several aspects remain unsolved. […] In conclusion, AMD shows a very intricate pathogenesis involving inflammation as a major cause of retinal damage and disease progression.

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