GENETIC ARCHITECTURE AND MOLECULAR BIOMARKERS OF PRIMARY OPEN-ANGLE GLAUCOMA: IMPLICATIONS FOR RISK STRATIFICATION AND PERSONALIZED THERAPY

Abstract

Introduction. Primary open-angle glaucoma (POAG) is a genetically heterogeneous optic neuropathy in which elevated intraocular pressure, retinal ganglion cell susceptibility, vascular regulation, extracellular-matrix remodeling, mitochondrial dysfunction, and immune signaling interact. Aim. To synthesize current evidence on monogenic variants, common polygenic susceptibility, molecular biomarkers, and emerging genotype-informed therapeutic strategies in POAG. Materials and methods. A narrative review was conducted using PubMed/MEDLINE-indexed publications identified with combinations of the terms “primary open-angle glaucoma,” “genetics,” “genome-wide association study,” “polygenic risk score,” “biomarker,” “proteomics,” “microRNA,” and “gene therapy.” Priority was given to multi-ancestry genetic studies, systematic reviews, longitudinal cohorts, and experimentally validated translational studies published through July 2026. Results. Rare variants in MYOC, OPTN, and TBK1 explain a small but clinically important fraction of familial or early-onset disease. Genome-wide analyses have identified hundreds of loci that converge on aqueous-outflow regulation, optic nerve development, vascular biology, extracellular matrix, and retinal ganglion cell survival. Polygenic risk scores are associated with disease onset, progression, and earlier need for surgery, but portability across ancestries remains limited. Candidate biomarkers in aqueous humor, tears, and blood include cytokines, complement proteins, oxidative-stress metabolites, neurotrophic factors, and microRNAs; none has yet achieved sufficient analytical and clinical validation for stand-alone diagnosis. Conclusion. The most realistic precision-medicine model combines ancestry-calibrated genetic risk, established ocular phenotypes, and longitudinal molecular markers. Clinical implementation requires prospective validation, standardized assays, and evidence that biomarker-guided decisions improve visual outcomes.