The interactions of genes, age, and environment in glaucoma pathogenesis

Abstract

Glaucoma, a progressive degenerative condition that results in the death of retinal ganglion cells, is one of the leading causes of blindness, affecting millions worldwide. The mechanisms underlying glaucoma are not well understood, although years of studies have shown that the largest risk factors are elevated intraocular pressure, age, and genetics. Eleven genes and multiple loci have been identified as contributing factors. These genes act by a number of mechanisms, including mechanical stress, ischemic/oxidative stress, and neurodegeneration. We summarize the recent advances in the understanding of glaucoma and propose a unified hypothesis for glaucoma pathogenesis. Glaucoma does not result from a single pathological mechanism, but rather a combination of pathways that are influenced by genes, age, and environment. In particular, we hypothesize that, in the presence of genetic risk factors, exposure to environment stresses results in an earlier age of onset for glaucoma. This hypothesis is based upon the overlap of the molecular pathways in which glaucoma genes are involved. Because of the interactions between these processes, it is likely that there are common therapies that may be effective for different subtypes of glaucoma.

Keywords: IOP; excitotoxicity; genetics; mechanical stress; neuroprotection; oxidative stress.