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Journal Francais D'ophtalmologie Sep 2020Glaucoma is a blinding optic neuropathy, the main risk factor for which is increased intraocular pressure (IOP). The trabecular meshwork, located within the iridocorneal... (Review)
Review
Glaucoma is a blinding optic neuropathy, the main risk factor for which is increased intraocular pressure (IOP). The trabecular meshwork, located within the iridocorneal angle, is the main pathway for drainage of aqueous humor (AH) out of the eye, and its dysfunction is responsible for the IOP elevation. The trabecular meshwork is a complex, fenestrated, three-dimensional structure composed of trabecular meshwork cells (TMC) interdigitated into a multilayered organization within the extracellular matrix (ECM). The purpose of this literature review is to provide an overview of current understanding of the trabecular meshwork and its pathophysiology in glaucoma. Thus, we will present the main anatomical and cellular bases for the regulation of aqueous humor outflow resistance, the pathophysiological mechanisms involved in trabecular dysfunction in the various types of glaucoma, as well as current and future therapeutic strategies targeting the trabecular meshwork.
Topics: Aqueous Humor; Glaucoma; Humans; Intraocular Pressure; Optic Nerve Diseases; Trabecular Meshwork; Trabeculectomy
PubMed: 32561029
DOI: 10.1016/j.jfo.2020.05.002 -
Acta Ophthalmologica May 2016Primary angle-closure glaucoma is potentially a devastating disease, responsible for half of glaucoma-related blindness worldwide. Angle closure is characterized by... (Review)
Review
Primary angle-closure glaucoma is potentially a devastating disease, responsible for half of glaucoma-related blindness worldwide. Angle closure is characterized by appositional approximation or contact between the iris and trabecular meshwork. It tends to develop in eyes with shallow anterior chambers, anteriorly positioned or pushed lenses, and angle crowding. Risk of primary angle-closure glaucoma is high among women, the elderly and the hyperopic, and it is most prevalent in Asia. Investigation into genetic mechanisms of glaucoma inheritance is underway. Diagnosis relies on gonioscopy and may be aided by anterior segment optical coherence tomography and ultrasound biomicroscopy. Treatment is designed to control intraocular pressure while monitoring changes to the angle and optic nerve head. Treatment typically begins with medical management through pressure-reducing topical medications. Peripheral iridotomy is often performed to alleviate pupillary block, while laser iridoplasty has been found effective for mechanisms of closure other than pupillary block, such as plateau iris syndrome. Phacoemulsification, with or without goniosynechialysis, both in eyes with existing cataracts and in those with clear lenses, is thus far a viable treatment alternative. Long-term research currently underway will examine its efficacy in cases of angle closure in early stages of the disease. Endoscopic cyclophotocoagulation is another treatment option, which can be combined with cataract surgery. Trabeculectomy remains effective therapy for more advanced cases.
Topics: Glaucoma, Angle-Closure; Gonioscopy; Humans; Intraocular Pressure; Iris; Risk Factors; Sex Factors; Trabecular Meshwork
PubMed: 26119516
DOI: 10.1111/aos.12784 -
International Journal of Medical... 2019Trabecular meshwork (TM) cells are a group of progenitors that have the ability to become adipocytes, chondrocytes and endothelial cells. Therefore, those adult corneal... (Review)
Review
Trabecular meshwork (TM) cells are a group of progenitors that have the ability to become adipocytes, chondrocytes and endothelial cells. Therefore, those adult corneal progenitors may be used as an effective therapy for trabecular meshwork diseases such as glaucoma, corneal endothelial dysfunctions such as blindness due to corneal endothelial dysfunction, and similar diseases. In order to promote the understanding of human trabecular meshwork progenitors, this article reviews human trabecular meshwork progenitor therapy and discusses its potential applications for curing human eye blindness.
Topics: Cell Differentiation; Endothelial Cells; Endothelium, Corneal; Glaucoma; Humans; Stem Cell Transplantation; Stem Cells; Trabecular Meshwork
PubMed: 31217738
DOI: 10.7150/ijms.32089 -
Experimental Eye Research Feb 2022In this review, we aim to provide a comprehensive summary of the various microRNAs (miRNAs) shown to be involved in glaucoma and intraocular pressure regulation. miRNAs... (Review)
Review
In this review, we aim to provide a comprehensive summary of the various microRNAs (miRNAs) shown to be involved in glaucoma and intraocular pressure regulation. miRNAs are short, single-stranded, and noncoding RNAs that regulate gene expression in a number of physiological conditions and human diseases, including glaucoma. Numerous miRNAs display differential expression in glaucoma-affected tissues, such as aqueous humor, tears, trabecular meshwork, and retina analyzed from patients and animal models, suggesting their potential involvement in glaucoma pathogenesis. Several studies summarized here have also investigated the challenge of delivering intact miRNAs to target tissues in order to develop miRNA-based glaucoma therapies. We extend these reports by conducting an additional layer of analysis that integrates the interaction between glaucoma-related miRNAs and glaucoma-associated genes. We conclude with a comprehensive discussion of the therapeutic potential of miRNAs, the cellular pathways that link these miRNAs together, and the most promising miRNAs for future glaucoma research.
Topics: Animals; Aqueous Humor; Glaucoma; Humans; Intraocular Pressure; MicroRNAs; Trabecular Meshwork
PubMed: 34968473
DOI: 10.1016/j.exer.2021.108909 -
Acta Ophthalmologica Jun 2022In a healthy eye, the aqueous humour (AH) flows via the ciliary body and trabecular meshwork into the collector channels, which carry it to the episcleral veins. In... (Review)
Review
In a healthy eye, the aqueous humour (AH) flows via the ciliary body and trabecular meshwork into the collector channels, which carry it to the episcleral veins. In glaucoma, a heterogeneous group of eye disorders affecting approximately 60 million individuals worldwide, the juxtacanalicular meshwork offers greater resistance to the outflow of the AH, leading to an increase in outflow resistance that gradually results in elevated intraocular pressure (IOP). The present review comprehensively covers the morphology of Schlemm's canal (SC) and AH pathways. The path of the AH from the anterior chamber through the trabeculum into suprascleral and conjunctival veins via collector channels is described, and the role of SC in the development of glaucoma and outflow resistance is discussed. Finally, channelography is presented as a precise method of assessing the conventional drainage pathway and facilitating localization of an uncollapsed collector and aqueous veins. Attention is also given to the relationship between aqueous and episcleral veins and heartbeat. Possible directions of future research are proposed.
Topics: Aqueous Humor; Glaucoma; Humans; Intraocular Pressure; Sclera; Trabecular Meshwork
PubMed: 34519170
DOI: 10.1111/aos.15027 -
Journal of Glaucoma 2014Trabecular meshwork (TM) and ciliary muscle contraction and relaxation function together to provide control of outflow. The active role the TM plays in the regulation of... (Review)
Review
Trabecular meshwork (TM) and ciliary muscle contraction and relaxation function together to provide control of outflow. The active role the TM plays in the regulation of intraocular pressure (IOP) is mediated by cytoskeletal and contractility mechanisms as well as signal/transduction factors that mediate its response to stressors. This complex system is altered with age and the glaucomas, and it can be difficult to differentiate between the various etiological effects/agents. Factors such as a compromised antioxidant defense system and altered extracellular matrix metabolism are known to contribute to impaired outflow and may be common to primary open-angle glaucoma, exfoliation syndrome, and exfoliation glaucoma (XFG). Genes differentially expressed in diseased ocular tissue or in cultured HTM cell models, and thus implicated in the disease process, include SOD2, ALDH1A1, MGST1, LOX, and LOXL1, elements of the transforming growth factor-β/bone morphogenetic protein/SMAD signaling pathways, connective tissue growth factor, matrix metalloproteinase-2, a tissue inhibitor of metalloproteinases also known as TIMP-2, and endothelin-1 (ET-1). In exfoliation syndrome and XFG fibrillar, proteinaceous extracellular material is produced in excess and accumulates in both outflow pathways but does not always lead to elevated IOP. Locally produced material may accumulate in the intertrabecular spaces, juxtacanalicular (JCT) meshwork, and the inner wall of Schlemm's canal as a result of a combination of both excessive synthesis and insufficient degradation. An increase in JCT plaque and decreased cellularity in the TM are thought to contribute to decreased outflow facility in glaucoma patients, but XFG patient specimens show reduced extracellular plaque material in the JCT, and the structural integrity of trabecular endothelial cells is mostly retained and cellularity remains unchanged. The distinctions between causes/effects of structural changes leading to reduced outflow/elevated IOP are important for developing effective, individualized treatment strategies.
Topics: Exfoliation Syndrome; Extracellular Matrix Proteins; Glaucoma, Open-Angle; Humans; Trabecular Meshwork
PubMed: 25275898
DOI: 10.1097/IJG.0000000000000106 -
Experimental Eye Research Jun 2017One of the major causes of decreased vision, irreversible vision loss and blindness worldwide is glaucoma. Increased intraocular pressure (IOP) is a major risk factor... (Review)
Review
One of the major causes of decreased vision, irreversible vision loss and blindness worldwide is glaucoma. Increased intraocular pressure (IOP) is a major risk factor associated with glaucoma and its molecular mechanisms are not fully understood. The trabecular meshwork (TM) is the primary site of injury in glaucoma, and its dysfunction results in elevated IOP. The glaucomatous TM has increased extracellular matrix deposition as well as cytoskeletal rearrangements referred to as cross-linked actin networks (CLANs) that consist of dome like structures consisting of hubs and spokes. CLANs are thought to play a role in increased aqueous humor outflow resistance and increased IOP by creating stiffer TM cells and tissue. CLANs are inducible by glucocorticoids (GCs) and TGFβ2 in confluent TM cells and TM tissues. The signaling pathways of these induction agents give insight into the possible mechanisms of CLAN formation, but to date, the mechanism of CLANs regulation by these pathways has yet to be determined. Understanding the role CLANs play in IOP elevation and their mechanisms of induction and regulation may lead to novel treatment options to help prevent or intervene in glaucomatous damage to the trabecular meshwork.
Topics: Actins; Aqueous Humor; Cells, Cultured; Glaucoma; Humans; Intraocular Pressure; Signal Transduction; Trabecular Meshwork
PubMed: 28238754
DOI: 10.1016/j.exer.2017.02.010 -
Experimental Eye Research May 2017With the combined purpose of facilitating useful vision over a lifetime, a number of ocular cells have evolved specialized features not found elsewhere in the body. The... (Review)
Review
With the combined purpose of facilitating useful vision over a lifetime, a number of ocular cells have evolved specialized features not found elsewhere in the body. The trabecular meshwork (TM) cell at the irido-corneal angle, which is a key regulator of intraocular pressure, is no exception. Examination of cells in culture isolated from the human TM has shown that they are unique in many ways, displaying characteristic features of several different cell types. Thus, these neural crest derived cells display expression patterns and behaviors typical of endothelia, fibroblasts, smooth muscle and macrophages, owing to the multiple roles and two distinct environments where they operate to maintain intraocular pressure homeostasis. In most individuals, TM cells function normally over a lifetime in the face of persistent stressors, including phagocytic, oxidative, mechanical and metabolic stress. Study of TM cells isolated from ocular hypertensive eyes has shown a compromised ability to perform their daily duties. This review highlights the many responsibilities of the TM cell and its challenges, progress in our understanding of TM biology over the past 30 years, as well as discusses unanswered questions about TM dysfunction that results in IOP dysregulation and glaucoma.
Topics: Animals; Aqueous Humor; Cell Culture Techniques; Glaucoma; Humans; Intraocular Pressure; Trabecular Meshwork
PubMed: 27443500
DOI: 10.1016/j.exer.2016.07.009 -
European Journal of Pharmacology Sep 2023Glaucoma is a chronic and progressive neurodegenerative disease characterized by the loss of retinal ganglion cells and visual field defects, and currently affects... (Review)
Review
Glaucoma is a chronic and progressive neurodegenerative disease characterized by the loss of retinal ganglion cells and visual field defects, and currently affects around 1% of the world's population. Elevated intraocular pressure (IOP) is the best-known modifiable risk factor and a key therapeutic target in hypertensive glaucoma. The trabecular meshwork (TM) is the main site of aqueous humor outflow resistance and therefore a critical regulator of IOP. Fibrosis, a reparative process characterized by the excessive deposition of extracellular matrix components and contractile myofibroblasts, can impair TM function and contribute to the pathogenesis of primary open-angle glaucoma (POAG) as well as the failure of minimally invasive glaucoma surgery (MIGS) devices. This paper provides a detailed overview of the current anti-fibrotic therapeutics targeting the TM in glaucoma, along with their anti-fibrotic mechanisms, efficacy as well as the current research progress from pre-clinical to clinical studies.
Topics: Humans; Trabecular Meshwork; Glaucoma, Open-Angle; Neurodegenerative Diseases; Intraocular Pressure; Glaucoma; Aqueous Humor
PubMed: 37391006
DOI: 10.1016/j.ejphar.2023.175882 -
Experimental Eye Research Jun 2018Cultured trabecular meshwork (TM) cells are a valuable model system to study the cellular mechanisms involved in the regulation of conventional outflow resistance and... (Review)
Review
Cultured trabecular meshwork (TM) cells are a valuable model system to study the cellular mechanisms involved in the regulation of conventional outflow resistance and thus intraocular pressure; and their dysfunction resulting in ocular hypertension. In this review, we describe the standard procedures used for the isolation of TM cells from several animal species including humans, and the methods used to validate their identity. Having a set of standard practices for TM cells will increase the scientific rigor when used as a model, and enable other researchers to replicate and build upon previous findings.
Topics: Age Factors; Animals; Biomarkers; Cell Culture Techniques; Cell Separation; Consensus; Fetus; Guidelines as Topic; Humans; Tissue Donors; Tissue Preservation; Tissue and Organ Harvesting; Trabecular Meshwork
PubMed: 29526795
DOI: 10.1016/j.exer.2018.03.001