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 second leading cause of irreversible blindness worldwide and is characterized by the optic nerve degeneration and loss of retinal ganglion cells (RGCs). This may lead to loss of vision. The primary cause of glaucoma 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 associated 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 degenerate. Several molecular signals such as oxidative stress, mitochondrial dysfunction, disruption of neurotrophic factor (NTF), dysfunction of immune system, glial activation and the release of tumor necrosis factor (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 factors may provide an opportunity to develop neuroprotective therapies and DNA based diagnostic tests.