Materiały źródłowe

• #1 The Pathophysiology and Treatment of Glaucoma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4523637/

  Glaucoma is a worldwide leading cause of irreversible vision loss. […] A general understanding of the disease pathophysiology, diagnosis, and treatment may assist primary care physicians in referring high-risk patients for comprehensive ophthalmologic examination and in more actively participating in the care of patients affected by this condition. […] To describe current evidence regarding the pathophysiology and treatment of open-angle glaucoma and angle-closure glaucoma. […] The glaucomas are a group of progressive optic neuropathies characterized by degeneration of retinal ganglion cells and resulting changes in the optic nerve head. Loss of ganglion cells is related to the level of intraocular pressure, but other factors may also play a role. […] Although the pathogenesis of glaucoma is not fully understood, the level of intraocular pressure is related to retinal ganglion cell death.

• #2 The Pathophysiology and Treatment of Glaucoma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4523637/

  The biological basis of glaucoma is poorly understood and the factors contributing to its progression have not been fully characterized. […] Glaucomatous optic neuropathy can occur in individuals with intraocular pressures within the normal range. […] Impaired microcirculation, altered immunity, excitotoxicity, and oxidative stress may also cause glaucoma. […] Primary neural pathological processes may cause secondary neurodegeneration of other retinal neurons and cells in the central visual pathway by altering their environment and increasing susceptibility to damage.

• #3

  https://journals.lww.com/ijo/fulltext/2009/57040/current_concepts_in_the_pathophysiology_of.2.aspx

  Glaucoma, the second leading cause of blindness, is characterized by changes in the optic disc and visual field defects. The elevated intraocular pressure was considered the prime factor responsible for the glaucomatous optic neuropathy involving death of retinal ganglion cells and their axons. Extensive investigations into the pathophysiology of glaucoma now reveal the role of multiple factors in the development of retinal ganglion cell death. A better understanding of the pathophysiological mechanisms involved in the onset and progression of glaucomatous optic neuropathy is crucial in the development of better therapeutic options. […] The pathophysiology of glaucomatous optic neuropathy is not well understood. Whether the site of primary damage is the ganglion cell body or their axons remains fiercely debatable. Irrespective of the initial site of neuronal injury and mechanisms involved, the terminal outcome is the death of RGCs and their axons leading to irreversible visual loss. This paper presents a review of the various mechanisms involved in the development of glaucomatous optic neuropathy.

• #4 The Pathophysiology and Treatment of Glaucoma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4523637/

  The balance between secretion of aqueous humor by the ciliary body and its drainage through 2 independent pathways—the trabecular meshwork and uveoscleral outflow pathway—determines the intra-ocular pressure. […] In patients with open-angle glaucoma, there is increased resistance to aqueous outflow through the trabecular meshwork. […] Intraocular pressure can cause mechanical stress and strain on the posterior structures of the eye, notably the lamina cribrosa and adjacent tissues. […] Intraocular pressure-induced stress and strain may result in compression, deformation, and remodeling of the lamina cribrosa with consequent mechanical axonal damage and disruption of axonal transport that interrupts retrograde delivery of essential trophic factors to retinal ganglion cells from their brainstem target.

• #5 Pathogenesis of Glaucoma

  https://www.mdpi.com/2673-8392/2/4/124

  Glaucoma, a neurodegenerative disease, has a varied pathogenesis scenario, including elevated intraocular pressure (IOP), and hypoxic conditions in the retina. Consequently, degenerating optic axons at the optic nerve head are observed clinically when extensive damage has already occurred. Following elevated IOP, changes in retinal ganglion cells lead to apoptosis immediately followed by degeneration of their optic axons. Degradation of axons leads to cupping of the optic nerve head and visual field losses. Here we emphasize that it is the retinal ganglion cells that are initial targets of elevated IOP, and, together with hyperactivity of retinal astrocytes, create the ischemic conditions which represent the earliest sign in the pathogenesis of glaucoma. […] Elevated IOP has been suspected to induce negative effects by the formation of a hypoxic environment in the eye following a reduction in ocular blood flow. Glaucomatous neurodegeneration is often preceded by a reduction of ocular perfusion due to decreased blood flow. Additionally, not all patients with glaucoma have elevated intraocular pressure, exemplified by normal tension glaucoma. Ischemia and histopathological glaucomatous abnormalities may occur in conditions of elevated IOP as well as in normal IOP conditions. The commonality in these conditions is the degeneration of retinal ganglion cells.

• #6 Glaucoma, Suspect, Adult: Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/1205421-overview

  The mechanisms that cause glaucoma are not fully understood. In most clinical cases, a painless elevation of IOP occurs, which can lead to progressive optic nerve damage and visual field loss. The mechanical theory of resistance to outflow (at the juxtacanicular meshwork) is one postulated mechanism for glaucoma. Disturbances of trabecular meshwork (TM) collagen, TM endothelial cell dysfunction, basement membrane thickening, glycosaminoglycan deposits, narrowing intertrabecular spaces, and/or collapse of the Schlemm canal may occur. Experimental and clinical studies show that sustained elevation of IOP can cause optic nerve damage similar to primary open-angle glaucoma (POAG), thus providing support for the role of IOP. […] Vascular risk factors and the role of optic nerve perfusion may be of importance. The blood supply to the optic nerve, the axonal or ganglion cell metabolism, and the lamina cribrosa extracellular matrix may play a role. This is especially important in a subgroup of individuals with low-tension glaucoma who have progressive disease despite IOP of less than 21 mm Hg.

• #7 Overview of Glaucoma – Eye Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/eye-disorders/glaucoma/overview-of-glaucoma

  Glaucomas are a group of eye disorders characterized by progressive optic nerve damage in which an important part is a relative increase in intraocular pressure (IOP) that can lead to irreversible loss of vision. […] Elevated intraocular pressure (IOP) plays a role in axonal damage, either by direct nerve compression or diminution of blood flow. […] IOP is determined by the balance of aqueous secretion and drainage. Elevated IOP is caused by inhibited or obstructed outflow, not oversecretion; a combination of factors in the trabecular meshwork (eg, dysregulation of extracellular matrix, cytoskeletal abnormalities) appear to be involved. In open-angle glaucoma, IOP is elevated because outflow is inadequate despite an angle that appears macroscopically unobstructed. In angle-closure glaucoma, IOP is elevated when the peripheral iris mechanically blocks outflow.

• #8 Angle-Closure Glaucoma – Eye Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/eye-disorders/glaucoma/angle-closure-glaucoma

  Angle-closure glaucoma is caused by factors that either pull or push the iris up into the angle (ie, junction of the iris and cornea at the periphery of the anterior chamber), physically blocking drainage of aqueous and raising intraocular pressure (IOP). Elevated IOP damages the optic nerve. […] Angle closure may be primary (cause is unknown) or secondary to another condition and can be acute, subacute (intermittent), or chronic. […] In people with narrow angles, the distance between the iris at the pupil and the lens is also very narrow. When the iris dilates, forces pull the iris centripetally and posteriorly, causing increasing iris-lens contact which prevents aqueous from passing between the lens and iris, through the pupil, and into the anterior chamber (this mechanism is termed pupillary block).

• #9 Glaucoma – Wikipedia

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

  Glaucoma is a group of eye diseases that can lead to damage of the optic nerve. The underlying cause of open-angle glaucoma remains unclear. Several theories exist on its exact etiology. Intraocular pressure is a function of production of liquid aqueous humor by the ciliary processes of the eye, and its drainage through the trabecular meshwork. In open/wide-angle glaucoma, flow is reduced through the trabecular meshwork, due to the degeneration and obstruction of the trabecular meshwork, whose original function is to absorb the aqueous humor. Loss of aqueous humor absorption leads to increased resistance and thus a chronic, painless buildup of pressure in the eye. […] In primary angle-closure glaucoma, the iridocorneal angle is narrowed or completely closed, obstructing the flow of aqueous humor to the trabecular meshwork for drainage. This accumulation of aqueous humor causes an acute increase in pressure and damage to the optic nerve.

• #10 Pathogenesis of Glaucoma

  https://www.mdpi.com/2673-8392/2/4/124

  The portion of the optic nerve head that is supported by the lamina cribrosa appears to be particularly susceptible to changes in IOP. This area is unique as it is the only location in the central nervous system where RGC axons do not have direct contact with local capillaries and therefore are heavily reliant on surrounding astrocytes for maintaining cellular health. […] Mechanical disruption of the extracellular environment by increased IOP results in astrocyte hypertrophy, thereby impeding the maintenance of RGC axon health and leaving these axons vulnerable. […] Retinal ganglion cell axons in the glaucomatous ONH exhibit several abnormalities which result in the degeneration of these axons. Studies have shown that in both animal models and humans, RGC axons in the ONH exhibit swelling. This axonal swelling has been proposed to represent the accumulation of transport vesicles, thereby demonstrating the dysfunctional retrograde and anterograde transport occurring in the ONH axons.

• #11 The Role of Ocular Blood Flow in the Pathogenesis of Glaucomatous Damage | touchOPHTHALMOLOGY

  https://touchophthalmology.com/glaucoma/journal-articles/the-role-of-ocular-blood-flow-in-the-pathogenesis-of-glaucomatous-damage/

  Ocular blood flow (OBF) is on average lower in glaucoma patients than in healthy controls. This reduction is more pronounced in normal-tension than in high-tension glaucoma and more distinct in cases with progressing damage as compared to those with stable disease. […] The fact that hypoxia-related factors are upregulated in eyes of glaucoma patients indicates oxygen depletion. It is, however, not constant hypoxia, but rather the fluctuation of oxygen supply that leads to tissue damage, likely because of oxidative stress. Low perfusion pressure and disturbed autoregulation are the major causes of insufficient and fluctuating oxygen supply, and both systemic hypotension and disturbed autoregulation are often consequences of the primary vascular dysregulation syndrome. […] It is obvious that blood flow is reduced in atrophic tissues. Therefore, that there is a secondary component is of little doubt. Interestingly, however, there are also many indications of a primary component. First of all, blood flow reduction can be observed in other parts of the body as well, such as in the nailfold capillaries, which obviously cannot be a consequence of glaucomatous damage. In addition, reduction of OBF often precedes further glaucomatous damage, which indicates that there must be an important primary component.

• #12 The Mechanism of Glaucomatous Damage to the Optic Nerve – touchOPHTHALMOLOGY

  https://touchophthalmology.com/glaucoma/journal-articles/the-mechanism-of-glaucomatous-damage-to-the-optic-nerve/

  The pathogenesis of glaucomatous damage involves activation of astrocytes and involvement of oxidative stress in the mitochondria, which are located numerously in the axons of the optic nerve head (ONH). […] The major cause of oxidative stress is unstable blood flow, which is unstable if either intraocular pressure (IOP) fluctuates on a high level, exceeding the capacity for autoregulation from time to time, or if autoregulation by itself is disturbed. […] The main cause of disturbed autoregulation is primary vascular dysregulation syndrome. […] The simultaneous production of superoxide anions and nitric oxide leads to the damaging peroxinitrite, which induces apoptosis. […] The activation of astrocytes leads to increased NO production. […] In parallel, recurrent mild reperfusion leads to the production of the superoxide anion (O2 .-) in the mitochondria, which is copiously located in the axons of the ONH.

• #13 The Mechanism of Glaucomatous Damage to the Optic Nerve – touchOPHTHALMOLOGY

  https://touchophthalmology.com/glaucoma/journal-articles/the-mechanism-of-glaucomatous-damage-to-the-optic-nerve/

  In this situation, the superoxide anion (O2 .-) can readily combine with NO to produce the highly damaging peroxynitrite (ONOO-), which in turn, induces apoptosis. […] Blood flow and, consequently, oxygen supply is unstable if IOP fluctuates at a relatively high level or if autoregulation is disturbed. […] The involvement of PVD explains why systemic hypotension in these subjects (but less so in others) is a risk factor for GON, why females suffer from NTG more often than males (females suffer more often from PVD) and why NTG occurs more often in the Japanese than in Caucasians (Japanese suffer more often from PVD). […] The above-described facts led to the following pathogenetic concept: both mechanical and ischaemic stress activate the glial cells, leading to an altered microenvironment, particularly in and around the ONH. […] This includes increased production of MMPs, which are involved in tissue remodelling.

• #14 The Role of Ocular Blood Flow in the Pathogenesis of Glaucomatous Damage | touchOPHTHALMOLOGY

  https://touchophthalmology.com/glaucoma/journal-articles/the-role-of-ocular-blood-flow-in-the-pathogenesis-of-glaucomatous-damage/

  Several independent studies demonstrated convincingly that a reduced OBF is, indeed, a risk factor for further progression. […] Both in the retina and in the optic nerve head of glaucoma patients, the hypoxia inducible factor 1 (HIF) is increased. […] Unstable OBF leads to unstable oxygen supply, which in turn triggers oxidative stress. An increased concentration of superoxide anions in an area where the production of nitric oxide (NO) is increased augments the production of the very damaging molecule peroxynitrite. […] The dysfunction of the autoregulation likely depicts the causal relationship between PVD and glaucomatous damage. […] In summary, unstable oxygen supply caused by IOP or blood pressure fluctuations or disturbed autoregulation leads to increased oxidative stress, a main contributor to glaucomatous damage.

• #15

  https://www.sciencebasedhealth.com/ContentPage.aspx?WebpageId=86&srsltid=AfmBOorPZ6FyYFZ6FhQV17wstqteNe1xIwUsX9zp4mlv_4uF4y-OCBII

  Glaucoma is the second leading cause of blindness in the world after cataracts. While research has identified non-pressure dependent risk factors for glaucoma, elevated intraocular pressure due to reduction in aqueous outflow remains a major causal factor. Several lines of evidence suggest that chronic oxidative stress is important in glaucoma pathogenesis: age-dependent clinical onset, constant exposure of the trabecular meshwork to H2O2 in the aqueous humor, and altered cellular and molecular responses to H2O2 exposure in vitro. Results of a recent investigation provide convincing evidence that oxidative damage to the trabecular meshwork is involved in glaucoma. […] Trabecular meshwork cells and the aqueous humor rely on antioxidant mechanisms for protection. In the meshwork for example, reduced glutathione protects against H2O2-induced oxidative damage, and it becomes depleted when the aqueous humor is under oxidative stress.

• #16 Pathogenesis of Glaucoma

  https://www.mdpi.com/2673-8392/2/4/124

  Increased intraocular pressure results in decreased retinal metabolic function, which leaves RGC axons vulnerable and results in eventual apoptosis. Retinal mitochondria, key cellular organelles involved in the axonal energetic support, become defective in glaucomatous models. Mitochondrial dysfunction is often attributed to the increased production of reactive oxygen species which interact with local molecules, such as mitochondrial DNA and cellular proteins, to inflict damage. As reactive oxygen species (ROS) accumulate and overwhelm the antioxidant capacity of the cell, a state of oxidative stress begins. Eventually, long-term exposure to oxidative stress induces apoptosis. Studies have indicated a strong correlation between the elevation of intraocular pressure and oxidative stress in retinal ganglion cell mitochondria.

• #17

  https://journals.lww.com/ijo/fulltext/2009/57040/current_concepts_in_the_pathophysiology_of.2.aspx

  The characteristic change in the optic nerve head in glaucoma is a cupping of the optic disc where ganglion cell axons have been lost. The death of the axons is associated with a loss of ganglion cell bodies in the retina and ganglion cell axon terminals in the dorsal lateral geniculate body. Death of RGCs in glaucomatous human eyes and experimental animal models of glaucoma takes place by apoptosis, which is also the means of eliminating 50% of the RGCs during normal developmental organization of the visual pathway. […] Until recently it was believed that elevated IOP plays a major role in RGC apoptosis and it is also true that reduction of elevated IOP often helps in slowing down the progression of degenerative changes in glaucoma. However, among glaucoma patients only one-third to half of all glaucoma patients have elevated IOP at the initial stages.

• #18

  https://journals.lww.com/ijo/fulltext/2009/57040/current_concepts_in_the_pathophysiology_of.2.aspx

  Elevated IOP often results from alterations in aqueous humor dynamics due to changes in trabecular meshwork leading to impaired drainage of aqueous. […] The primary mechanism of neuronal loss in the initial phase is apoptosis while in the second phase neuronal loss is due to toxic effects of the primary degenerating neurons in addition to continuing exposure to elevated IOP. […] Cellular responses to changes in IOP, leading to apoptosis of RGCs are not well understood. A possible mechanism of RGC apoptosis seems to be related to changes in extracelluar matrix components in the retina of glaucomatous eyes in response to elevated IOP. […] The molecular mechanisms leading to RGC death due to vascular dysregulation are not clearly understood. The vascular insufficiency can directly damage and cause RGC apoptosis.

• #19

  https://journals.lww.com/ijo/fulltext/2009/57040/current_concepts_in_the_pathophysiology_of.2.aspx

  Apoptotic cell death of RGCs has also been attributed to glutamate-mediated toxicity and upon exposure to hypoxic conditions retinal cells are known to release glutamate. […] Nitric oxide plays an important and beneficial role in body function when secreted in physiological quantities, however, excess production of NO has been associated with a variety of non-neurological and neurological conditions including glaucoma. […] The excessive formation of free radicals and oxidative stress is recognized as an etiopathogenetic factor in many ocular diseases such as cataract, age-related macular degeneration and more recently glaucoma. […] To summarize, the primary factors responsible for apoptotic cell death in glaucoma include not only elevated IOP but also vascular dysregulation, especially in people with NTG. The molecular mechanisms involved largely include glutamate excitotoxicity, increased MMP expression, TNF-alpha upregulation, increased NOS-2 expression and oxidative stress.

• #20 The pathogenesis of glaucoma in the interplay with the immune system – PubMed

  https://pubmed.ncbi.nlm.nih.gov/23539162/

  Glaucoma was previously thought to be caused only through an elevated intraocular pressure as a sole trigger. Emerging evidence indicates that the pathogenesis of glaucoma depends on several interacting pathogenetic mechanisms, which include mechanical effects by an increased IOP, decreased neutrophine-supply, hypoxia, excitotoxicity, oxidative stress and the involvement of autoimmune processes. […] These autoimmune processes within the central nervous system are a highly organized response of the innate immunity. Through the recognition of neuronal epitopes, the long-term induction of the innate immune response and its transition to an adaptive form might be central to the pathophysiology of the glaucoma disease. […] Regardless of the pathogenic mechanism, the consequences are always the establishment of extensive degenerative processes in the optic nerve head, the retinal ganglion cells and the axons of the optic nerve, which will lead in the irreversible destruction of these neurons. This review article summarizes the current knowledge concerning the pathogenesis of glaucoma, with special focus on its interplay with the immune system.

• #21 A Novel Mathematical Model of Glaucoma Pathogenesis

  https://www.jocgp.com/abstractArticleContentBrowse/JOCGP/16498/JPJ/fullText

  Background: Conventional experimental approaches to understand glaucoma etiology and pathogenesis and, consequently, predict its course of progression have not seen much success due to the involvement of numerous molecular, cellular, and other moieties. […] Our results suggest that microglia activation is among the earliest events in glaucoma pathogenesis. […] We here report the first mathematical model for glaucoma pathogenesis which provides important insight into the sensitivity coefficient and glia-mediated pathology of glaucoma. […] Neuroglia interaction mediated through inflammation is one of the common denominators of pathways involved in glaucoma pathogenesis. […] Our model suggests that microglial activation is one of the earliest events in glaucoma which is in agreement with the previously published literature.

• #22 A Novel Mathematical Model of Glaucoma Pathogenesis

  https://www.jocgp.com/abstractArticleContentBrowse/JOCGP/16498/JPJ/fullText

  This equation suggests a microglia-mediated switch in RGC priming for apoptosis. […] The present study is the first mathematical model developed for neuronglia interaction in glaucoma. […] The proposed mathematical model may be useful in understanding the pathogenesis and neuronglia interaction in glaucoma. […] The etiopathomechanism of glaucoma involves many moieties in addition to RGCs and glia.

• #23 Primary open angle glaucoma genetics: The common variants and their clinical associations (Review)

  https://www.spandidos-publications.com/10.3892/mmr.2020.11215

  POAG has long shown a strong genetic component with 60% of patients with a positive family history and family based studies identifying a 10-fold increased risk of POAG for first degree relatives. […] Heritability of POAG can be divided into two major categories: direct association (increased POAG risk) and indirect (increased risk for a component of the disease). […] The first one deals with several genes linked to POAG through family-based genetic linkage analysis, with major examples being myocilin (MYOC), optineurin (OPTN), WD repeat domain 36 (WDR36), cytochrome P450, family 1, subfamily B, polypeptide 1 (CYP1B1) and neurotrophin 4 (NTF4). […] Genome-wide association studies (GWAS) have been used in the past decade in an attempt to uncover genetic variants of complex diseases. […] For POAG, over 70 single-nucleotide polymorphisms (SNPs) have been identified and linked to POAG or its endophenotypes, changing our understanding of the molecular pathways of the disease.

• #24 Glaucoma: Etiology, Pathophysiology and Management

  https://biomedres.us/fulltexts/BJSTR.MS.ID.005005.php

  Oxidative stress excitotoxicity altered immunity and impaired microcirculation may cause glaucoma. […] Death of neurons, growth and differentiation of neurons is regulated by neurotrophins or neurotrophic factors (NTF). […] Decrease in NTF results in RGC apoptosis. […] Glaucoma is associated with genetic/congenital eye malformations. Mutations at several loci of genes are associated with glaucoma. […] One third of POAG is comprised of normal tension Glaucoma and it is also linked to genetic mutations. […] The occurrence of COAG elevates with age. […] Without any symptoms or pain pressure builds up with in the eye, results to initiate the loss of vision of peripherally of eye. […] It is a surgical method utilized to treat glaucoma. […] Aqueous shunt devices (glaucoma implants or tubes) are synthetic drainage devices are employed to low the IOP in the eye. […] These drops are utilized to decrease eye pressure, either by decreasing the amount of fluid it produces or increasing the eyes ability to drain.

• #25 Glaucoma Pathogenesis and Neurotrophins: Focus on the Molecular and Genetic Basis for Therapeutic Prospects

  https://benthamscience.com/public/article/89844

  Retinal ganglion cell (RGC) degeneration is a major feature of glaucoma pathology. […] The aim of this review was to examine the progress in genetics and cellular mechanisms associated with endoplasmic reticulum (ER) stress, RGC dysfunction and cell death pathways in glaucoma. […] The literature review of the neurobiology underlying neurotrophin pathways, ER stress and gene associations provide critical insights into association of RGCs death in glaucoma. […] Several genes that are linked with neurotrophin signalling pathways have been reported to be associated with glaucoma pathology. […] Understanding genetic heterogeneity and involvement of neurotrophin biology in glaucoma could help to understand the complex pathophysiology of glaucoma. Identification of novel molecular targets will be critical for drug development and provide neuroprotection to the RGCs and optic nerve.

• #26 Role of Glucocorticoids and Glucocorticoid Receptors in Glaucoma Pathogenesis

  https://www.mdpi.com/2073-4409/12/20/2452

  The glucocorticoid receptor (GR), including both alternative spliced isoforms (GRα and GRβ), has been implicated in the development of primary open-angle glaucoma (POAG) and iatrogenic glucocorticoid-induced glaucoma (GIG). […] One serious side effect of prolonged GC therapy is the development of iatrogenic secondary ocular hypertension (OHT) and OAG (i.e., GC-induced glaucoma (GIG)) that clinically and pathologically mimics POAG. […] GC-induced OHT is caused by pathogenic damage to the trabecular meshwork (TM), a tissue involved in regulating aqueous humor outflow and intraocular pressure. […] Almost all POAG patients develop GC-OHT when treated with GCs, in contrast to a GC responder rate of 40% in the normal population. […] A number of studies have suggested increased levels of endogenous cortisol in POAG patients as well as differences in cortisol metabolism, suggesting that GCs may be involved in the development of POAG.

• #27 Role of Glucocorticoids and Glucocorticoid Receptors in Glaucoma Pathogenesis

  https://www.mdpi.com/2073-4409/12/20/2452

  The TM functions as a biological sieve, which filters and drains the aqueous humor out of the eye while maintaining optimal physiological IOP. GCs induce a number of changes to TM cells. […] GCs contribute to increased TM resistance by increasing expression and extracellular deposition of fibronectin, glycosaminoglycans (GAGs), elastin, collagen, and laminin within the trabecular meshwork tissue. […] The clinical and pathological manifestations of GIG closely resemble POAG. […] Despite considerable research, the exact molecular mechanism(s) responsible for GC-induced IOP elevation observed in GIG remains unknown. […] The elevated IOP in POAG and GC-OHT is due to pathogenic damage to the trabecular meshwork (TM), and a tissue at the iridocorneal angle that regulates IOP. […] The ratio of these two isoforms makes TM cells more responsive (low GRβ) or less responsive (high GRβ) to GCs. […] Insights into the molecular mechanisms responsible for GC-OHT may also lead to the discovery of pathogenic pathways playing a role in the development of POAG.

• #28 Normal tension glaucoma: review of current understanding and mechanisms of the pathogenesis | Eye

  https://www.nature.com/articles/s41433-018-0042-2

  Normal tension glaucoma (NTG) is an exception in the glaucoma family where the major risk factor, increased intraocular pressure, is missing. If not increased intraocular pressure, then what other causes can then lead to glaucomatous optic disc change and visual field loss in NTG? Several possibilities will be discussed. Among them a higher sensitivity to normal pressure, vascular dysregulation, an abnormally high translaminar pressure gradient and a neurodegenerative process due to impaired cerebrospinal fluid dynamics in the optic nerve sheath compartment. […] The fact that several concepts exist suggests that NTG is still not very well understood and that no single mechanism on its own might adequately explain NTG. […] The fact that none of these theories is able to render an all conclusive and unanimous explanation for NTG, demonstrates that the pathophysiology of NTG might be multifactorial.

• #29 Clues to the Complex Pathogenesis of Glaucoma

  https://www.managedhealthcareexecutive.com/view/clues-to-the-complex-pathogenesis-of-glaucoma

  Researchers using data from prospective cohort studies identify higher levels of diglycerides and triglycerides in the blood as possibly playing an important role in the multifactorial causation of glaucoma. […] But Oana A. Zeleznik, Ph.D., a researcher at Brigham and Womens Hospital in Boston, and her colleagues have found that higher levels of diglycerides and triglycerides in the blood are adversely associated with glaucoma, suggesting that they play an important role in the pathogenesis. […] The findings, they argue, indicate that lipid dysregulation and mitochondrial function play an important role in causing glaucoma and might lead to new targets for prevention or treatment.

• #30

  https://journals.lww.com/mgmj/fulltext/2023/04000/impact_of_trace_elements_and_risk_factor_for.26.aspx

  Glaucoma is a multifunctional disease with several trace elements associated with its pathophysiology. […] A study of a significant amount of literature suggests that several trace element elements are associated with intraocular pressure (IOP), trabecular meshwork, and optical nerve oxidative stress changes in complex eye diseases. […] The etiology of glaucoma is multifactorial with several possible concomitant factors, including glutamate excitotoxicity including vascular changes, interrupted retrograde transport of neurotrophins, ocular ischemia, and oxidative stress (OS). […] Several lines of evidence suggest that OS and free radical accumulation harm the trabecular meshwork (TM), resulting in increased IOP, and damages retinal ganglion cells (RGCs), resulting in cell death that leads to ON damage, a characteristic of glaucoma.

• #31

  https://journals.lww.com/mgmj/fulltext/2023/04000/impact_of_trace_elements_and_risk_factor_for.26.aspx

  Surface abnormality ratio is a significant factor in the first phase of glaucoma pathogenesis (high-tension glaucoma), in which free radicals affect the TM endothelial cells and cause morphologic and functional changes and undergo diffuse injury. […] Following this condition, mitochondrial OS increases, leading to the excretion of the whole TM and accelerated IOP. […] In addition, evidence from population studies suggests that trace metal concentrations in the body could affect the balance between oxidants and antioxidants in glaucoma pathogenesis. […] Trace elements are dietary minerals belonging to the list of micronutrients required in tiny amounts as essential for the organisms proper growth, production, and physiology. […] Specifically, lower levels of manganese (Mn) in the blood and higher levels of serum mercury and ferritin are associated with an increased likelihood of glaucoma.

• #32

  https://journals.lww.com/mgmj/fulltext/2023/04000/impact_of_trace_elements_and_risk_factor_for.26.aspx

  A correlation exists between low Cr levels and an increased risk of glaucoma. […] Lead (Pb) is an environmental toxicant that ROS production may cause OS, which has been identified as a significant mechanism underlying Pb toxicity. […] High concentrations of Zn are found inside the retina, suggesting its essential function in this tissue. […] Trace elements are implicated in modifications mediated by OS, thus possibly involved in glaucoma pathogenesis. […] The increased levels and accumulation of trace elements in the eyes may play a role in the pathogenesis of glaucoma. […] The role of trace elements in glaucoma development is multiple and rather complex; some features can be protective, and others can act as promoters. […] However, we must undertake epidemiological and experimental investigations to establish whether these factors genuinely affect the course of ocular hypertension and glaucoma.

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