Genetic complexity of primary open-angle glaucoma

Abstract

Glaucoma is a complex genetic optic disease characterized by a range of optic neuropathies. There are many subtypes of glaucoma but primary open-angle glaucoma (POAG) associated with elevated intraocular pressure (IOP) is the most prevalent form. Based on the age of diagnosis, POAG is categorized as early-onset POAG or juvenile open-angle glaucoma (JOAG) diagnosed between 10 and 35 years and adult-onset POAG (APOAG) diagnosed in the fifth or sixth decade of life. Employing genetic tools like genome wide linkage analysis, association studies, mutation analysis, microarray expression analysis and serial analysis of gene expression at least 26 genetic loci have been identified for POAG but only three causative genes (Myocilin, Optineurin and WDR36) have been discovered till date. Sequence alterations in these genes result in or increase the likelihood of getting this disease than normal subjects. Although currently 5% of the POAG cases are linked to mutations in these three genes, more than 32 genes are identified to be associated with POAG. Like many other complex diseases gene environment interaction plays a pivotal role in the pathogenesis of POAG also. Lifestyle modifications, quality of diet, level of exercise and oxidative stress are the major risk factors influencing the severity and likelihood of POAG. Intense studies are required to find new genes and genetic defects related to POAG and the role of environment on the POAG pathogenesis. These initiatives can give new horizons to the diagnosis and clinical management of POAG.