Molecular genetics of primary open-angle glaucoma

Yadav, Manoj Kumar; Bhardwaj, Aarti; Yadav, Anshu; Dada, Rima; Tanwar, Mukesh

doi:10.4103/ijo.ijo_2570_22

Cited by 5 publications

(3 citation statements)

References 181 publications

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“…MYOC, the gene that encodes myocilin, is a genetic risk factor for glaucoma. Myocilin is thought to play a role in extracellular matrix remodeling in the TM, although this is an area of ongoing research [8]. This alteration in TM functionality and impaired aqueous humor drainage may be exacerbated by glucocorticoid-mediated TM dysfunctions.…”

Section: Glucocorticoids and Intraocular Pressure (Iop)mentioning

confidence: 99%

“…However, unlike other neurodegenerative diseases, the retinal microenvironment in glaucoma differs from the rest of the central nervous system (CNS), as it is a relatively immune-privileged site [3,6,7]. Despite this, one of the major genes implicated in the risk of glaucoma is TBK1, which is involved in the innate immune response, suggesting inflammatory and immunomodulatory components to the disease pathogenesis [8].…”

Section: Introductionmentioning

confidence: 99%

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Stress, Allostatic Load, and Neuroinflammation: Implications for Racial and Socioeconomic Health Disparities in Glaucoma

McDermott,

Salowe,

Di Rosa

et al. 2024

IJMS

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Glaucoma is the leading cause of irreversible blindness, and its pathophysiology includes neuroinflammatory changes. The present therapies for glaucoma target pressure-lowering mechanisms with limited success, making neuroinflammation a target for future interventions. This review summarizes the neuroinflammatory pathways seen in glaucoma and their interplay with stress. Glucocorticoids have been shown to activate proinflammatory glial cells, contributing to the neuroinflammation in glaucoma. Glucocorticoids have also been shown to increase the IOP directly. Stress-associated autonomic dysfunction can affect the vascular homeostasis in the retina and create oxidative stress. Diabetes, hyperglycemic-mediated endothelial damage, and vascular inflammation also play important roles in the neuroinflammation in glaucoma and diabetic retinopathy. Psychosocial stress has been implicated in an increased IOP and glaucoma outcomes. People who experience maladaptive chronic stress suffer from a condition known as allostatic load, which describes pathologic neuroendocrine dysregulation. The effects of allostatic load and chronic stress have been studied in patients affected by a lower socioeconomic status (SES) and marginalized racial identities. A lower SES is associated with higher rates of glaucoma and also affects the access to care and screening. Additionally, people of African ancestry are disproportionately affected by glaucoma for reasons that are multifactorial. In conclusion, this review explores neuroinflammation in glaucoma, highlighting opportunities for future investigation.

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Section: Glucocorticoids and Intraocular Pressure (Iop)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Stress, Allostatic Load, and Neuroinflammation: Implications for Racial and Socioeconomic Health Disparities in Glaucoma

McDermott,

Salowe,

Di Rosa

et al. 2024

IJMS

View full text Add to dashboard Cite

show abstract

“…Glaucoma, a leading cause of irreversible blindness and visual impairment, is characterized by the progressive degeneration of retinal ganglion cells (RGCs) and the thinning of the retinal nerve fiber layer (RNFL), resulting in gradual visual field loss [1][2][3]. Reported risk factors for glaucoma, based on clinical trials, include elevated intraocular pressure (IOP), advanced age, race, myopia, optic nerve susceptibility, and positive family history [1,2].…”

Section: Introductionmentioning

confidence: 99%

Profile of Lipoprotein Subclasses in Chinese Primary Open-Angle Glaucoma Patients

Fu,

Xu,

Chen

et al. 2024

IJMS

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To investigate the plasma lipoprotein subclasses in patients with primary open-angle glaucoma (POAG), a total of 20 Chinese POAG patients on intraocular pressure (IOP)-lowering treatment and 20 age-matched control subjects were recruited. Based on the levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), the study subjects were divided into elevated- and normal-level subgroups. The plasma lipoprotein, lipoprotein subclasses, and oxidized LDL (oxLDL) levels were quantitatively measured. The discrimination potential of the lipoproteins was evaluated using the area under the receiver operating characteristic curve (AUC), and their correlation with clinical parameters was also evaluated. Compared to the control subjects with elevated TC and/or LDL-C levels, the levels of TC, LDL-C, non-high-density lipoprotein cholesterol (non-HDL), LDL subclass LDL3 and small dense LDL (sdLDL), and oxLDL were significantly higher in POAG patients with elevated TC and/or LDL-C levels. No differences in any lipoproteins or the subclasses were found between the POAG patients and control subjects with normal TC and LDL-C levels. Moderate-to-good performance of TC, LDL-C, non-HDL, LDL3, sdLDL, and oxLDL was found in discriminating between the POAG patients and control subjects with elevated TC and/or LDL-C levels (AUC: 0.710–0.950). Significant negative correlations between LDL3 and sdLDL with retinal nerve fiber layer (RNFL) thickness in the superior quadrant and between LDL3 and average RNFL thickness were observed in POAG patients with elevated TC and/or LDL-C levels. This study revealed a significant elevation of plasma lipoproteins, especially the LDL subclasses, in POAG patients with elevated TC and/or LDL-C levels, providing insights on monitoring specific lipoproteins in POAG patients with elevated TC and/or LDL-C.

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Identification of Optic Nerve–Related Biomarkers in Primary Open-Angle Glaucoma Based on Comprehensive Bioinformatics and Mendelian Randomization

Zhao,

Dai,

Rao

et al. 2024

Trans. Vis. Sci. Tech.

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Purpose Glaucoma is the primary cause of permanent vision loss worldwide. However, the pathogenesis of primary open-angle glaucoma (POAG), the main type of glaucoma, has not yet been completely understood. Methods In our study, the POAG cohorts were obtained from the Gene Expression Omnibus (GEO) database (GSE45570). Biomarkers with diagnostic utility for POAG were identified through combining differentially expressed analysis, enrichment analysis, machine learning algorithms, and receiver operating characteristic (ROC) analysis. The regulatory networks (including a competing endogenous RNA (ceRNA) regulatory network and a small molecule compounds-mRNA network) were created. In addition, the Mendelian randomization (MR) analysis was used to identify exposures causally associated with POAG. Finally, the expression of the biomarkers was validated via real-time quantitative polymerase chain reaction (RT-qPCR). Results The Gene Ontology (GO) items that the differentially expressed genes (DEGs) between POAG and control groups enriched were relevant to light stimulation and DNA methylation. A total of three light stimulation-related biomarkers ( RAB8A , PRG3 , and SMAD3 ) were identified, which had diagnostic value for POAG patients. Besides, the ceRNA regulatory network contained 88 nodes and 93 edges, and a small molecule compounds-mRNA network included 66 nodes and 76 edges. The MR results indicated a causal association between DNA methylation GrimAge acceleration and POAG. Additionally, the results of RT-qPCR revealed that the expression trend of RAB8A was consistent with that of GSE45570. Conclusions Taken together, this study provides three light stimulation-related biomarkers ( RAB8A , PRG3 , and SMAD3 ) for the diagnosis of POAG, providing scientifically valuable insights for further studies of POAG. Translational Relevance Discovering biomarkers that possess diagnostic significance for POAG has the potential to offer new insights into the pathogenesis of POAG and present novel objectives for clinical intervention.

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Molecular genetics of primary open-angle glaucoma

Cited by 5 publications

References 181 publications

Stress, Allostatic Load, and Neuroinflammation: Implications for Racial and Socioeconomic Health Disparities in Glaucoma

Stress, Allostatic Load, and Neuroinflammation: Implications for Racial and Socioeconomic Health Disparities in Glaucoma

Profile of Lipoprotein Subclasses in Chinese Primary Open-Angle Glaucoma Patients

Identification of Optic Nerve–Related Biomarkers in Primary Open-Angle Glaucoma Based on Comprehensive Bioinformatics and Mendelian Randomization

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