Genetic risk factors and retinal ganglion cell degeneration in primary open-angle glaucoma (POAG): A bird’s eye view

Abstract

Glaucoma is an optic neuropathy and often associated with elevated intraocular pressure (IOP). It is the se-cond leading cause of irreversible blindness world-wide and is characterized by the optic nerve degen-eration and loss of retinal ganglion cells (RGCs). This may lead to loss of vision. The primary cause of glau-coma is unknown but several risk factors including elevated IOP and age have been suggested. In most population, primary open-angle glaucoma (POAG) is the most common type of glaucoma and is often asso-ciated with elevated IOP. Genetic analyses have iden-tified at least 14 chromosomal loci but only three genes which when mutated can cause POAG have been well documented. These genes account for less than 5% of all POAG cases suggesting that more than 90% of the genetic contribution of POAG cases is unknown. RGC consists of cell body, axon and dendritic arbor and each of these three parts can independently degener-ate. Several molecular signals such as oxidative stress, mitochondrial dysfunction, disruption of neurotro-phic factor (NTF), dysfunction of immune system, glial activation and the release of tumor necrosis fac-tor (TNF) have been found to be involved in the optic nerve degeneration. Therefore, therapies aimed at axonal and cell body protection may have a greater protective role in early or progressive glaucoma. In the future, an understanding of gene-gene and gene-environmental factor interaction as well as epigenetic regulation of gene expression by environmental fac-tors may provide an opportunity to develop neuro-protective therapies and DNA based diagnostic tests.