Glaucoma is one of the world's leading causes of irreversible blindness. A complex, multifactorial disease, the underlying pathogenesis and reasons for disease progression are not fully understood. The most common form of glaucoma, primary open-angle glaucoma (POAG), was traditionally understood to be the result of elevated intraocular pressure (IOP), leading to optic nerve damage and functional vision loss. Recently, researchers have suggested that POAG may have an underlying genetic component. In fact, studies of genetic association and heritability have yielded encouraging results showing that glaucoma may be influenced by genetic factors, and estimates for the heritability of POAG and disease-related endophenotypes show encouraging results. However, the vast majority of the underlying genetic variants and their molecular mechanisms have not been elucidated. Several genes have been suggested to have molecular mechanisms contributing to alterations in key endophenotypes such as IOP (LMX1B, MADD, NR1H3, and SEPT9), and VCDR (ABCA1, ELN, ASAP1, and ATOH7). Still, genetic studies about glaucoma and its molecular mechanisms are limited by the multifactorial nature of the disease and the large number of genes that have been identified to have an association with glaucoma. Therefore, further study into the molecular mechanisms of the disease itself are required for the future development of therapies targeted at genes leading to POAG endophenotypes and, therefore, increased risk of disease.
Keywords: cup-to-disc ratio; genetics; glaucoma; heritability; intraocular pressure; primary open-angle glaucoma.