| Glaucoma is one of the most common, multifactorial neurodegenerative disease characterized by various clinical manifestations, involving retinal ganglion cell (RGC) loss and degeneration of the optic nerve. Elevated intraocular pressure (IOP) is a major risk factor, but disease outcome is affected by many other factors whose molecular effects are not well defined. Recent genome-wide association studies (GWAS) have advanced our understanding of genetic factors that underlie pathogenesis and progression of glaucoma.
The findings of GWAS in glaucoma are promising in following aspects: (1) New genetic factors in pathogenesis of glaucoma, such as CAV1 and CAV2 genes were found expressed in trabecular meshwork and retinal ganglion cells and were involved in pathogenesis of POAG in Iceland population, and was replicated in large sample sets from Sweden, the UK and Australia, and Hong Kong and Chinese. Two nonsynonymous SNPs in exon 1 of LOXL 1 were associated with exfoliation glaucoma through exfoliation syndrome in Iceland, Sweden and combined cohorts. (2) Drug targeting and development for glaucoma: GWAS on DAB/2J mouse, a model of pigmentary glaucoma revealed up-regulation of the complement cascade and the endothelin system as molecular events happened at early stages of glaucoma. Inhibition of the endothelin system was strongly protective against glaucomatous damage. Targeting early molecular events may provide effective new treatment for human glaucoma. In this study, author reviews these finding of GWAS in glaucoma, which may lead a new era for glaucoma research and management. |
