EVALUATION OF THE GENETIC ETIOLOGIES OF GLAUCOMA

Abstract

Introduction: Glaucoma is one of the leading causes of irreversible blindness worldwide, characterized by a heterogeneous group of progressive optic neuropathies associated, in most cases, with elevated intraocular pressure. In recent decades, genetic studies have shown that hereditary factors play a determining role in the development and progression of the disease, especially in early-onset and familial forms. Research has shown that mutations in genes such as MYOC, OPTN, and CYP1B1 are directly associated with impairment of the trabecular meshwork and the aqueous humor drainage pathway, triggering structural changes in the optic nerve. Objective: To identify and analyze the main scientific evidence available in the last 10 years regarding the genetic etiologies associated with glaucoma, gathering data that clarify the contribution of different genes and molecular mechanisms in the development of the disease. Methodology: The research followed the recommendations of the PRISMA checklist. Searches were conducted in PubMed, Scielo, and Web of Science databases using the descriptors "glaucoma," "genetics," "etiology," "genes," and "polymorphism." Original articles, reviews, and cohort studies addressing the relationship between genetic factors and glaucoma, published in the last 10 years and available in Portuguese, English, or Spanish, were included. Studies with small sample sizes, research without direct genetic analysis, and opinion articles without primary data were excluded. Results: The studies analyzed demonstrated that mutations in CYP1B1 were strongly associated with primary congenital glaucoma, while alterations in MYOC were predominant in juvenile and early-onset forms. Polymorphisms in OPTN and TBK1 were associated with open-angle glaucoma, suggesting mechanisms of axonal degeneration mediated by inflammatory and apoptotic pathways. The literature reinforces that understanding the genetic basis of glaucoma has enabled advances in diagnostic biomarkers, in addition to opening up prospects for gene therapies and targeted pharmacological interventions. Conclusion: It was concluded that genetic etiologies play a central role in the pathogenesis of glaucoma, directly impacting diagnosis, prognosis, and prevention strategies.