The loss of retinal ganglion cells, the outcome of a set of eye illnesses known together as glaucoma, is the primary cause of permanent blindness worldwide. In addition to being older and having a family history of glaucoma, increased intraocular pressure (IOP) is a key risk factor. The anterior chamber angle is open, but aqueous outflow is blocked in primary open-angle glaucoma (POAG). Crowding of the anterior chamber angle due to anatomical abnormalities impedes aqueous outflow via the angle in primary angle-closure glaucoma (PACG). In addition, the deposition of white flaky debris in the anterior chamber directly interferes with aqueous outflow in exfoliation syndrome and exfoliation glaucoma. Researchers have found that a significant genetic component contributes to both the development and progression of glaucoma in observational studies. More than 100 genetic markers have been identified as being linked to glaucoma risk, resulting from a series of genome-wide association studies (GWAS) focused on single nucleotide polymorphisms (SNPs). However, the challenge of isolating the true effector genes responsible for disease pathogenesis is a limitation of GWAS investigations. Research groups have recently performed whole exome sequencing to assess the role of genetic polymorphisms in coding sequences that change proteins in relation to glaucoma risk, building on the foundation built by GWAS investigations. Adopting this technology in both large population-based investigations and family studies is uncovering the presence of novel, protein-changing genetic variations that may improve the understanding of the pathophysiology of glaucoma. Primary open-angle glaucoma, primary angle-closure glaucoma, and exfoliation glaucoma account for the great majority of glaucoma cases worldwide, and this study will focus on current developments in the genetics of these 3 types of glaucoma. To describe how the risk conveyed by a genetic sequence variant manifests itself in patients, it will be discussed how recent breakthroughs in research methods have identified novel risk genes and how subsequent biological investigations could be done. In addition, it will also be speculated how the information gleaned from characterizing these genetic variants could be used to predict glaucoma risk and how it could inform the development of novel therapeutic approaches.

Source: sciencedirect.com/science/article/abs/pii/S135094622200026X