Elevated Intraocular Pressure and Glaucomatous Optic Neuropathy: Genes to Disease Mechanisms, Therapeutic Drugs, and Gene Therapies

Abstract

This review article focuses on the pathogenesis of and genetic defects linked with chronic ocular hypertension (cOHT) and glaucoma. The latter ocular disease constitutes a group of ocular degenerative diseases whose hallmark features are damage to the optic nerve, apoptotic demise of retinal ganglion cells, disturbances within the brain regions involved in visual perception and considerable visual impairment that can lead to blindness. Even though a number of pharmaceuticals, surgical and device-based treatments already exist addressing cOHT associated with the most prevalent of the glaucoma types, primary open-angle glaucoma (POAG), they can be improved upon in terms of superior efficacy with reduced side-effects and with longer duration of activity. The linkage of disease pathology to certain genes via genome-wide associated studies are illuminating new approaches to finding novel treatment options for the aforementioned ocular disorders. Gene replacement, gene editing via CRISPR-Cas9, and the use of optogenetic technologies may replace traditional drug-based therapies and/or they may augment existing therapeutics for the treatment of cOHT and POAG in the future.

Keywords

• primary open-angle glaucoma
• genome-wide associated studies (GWAS)
• ocular hypertension
• optogenetics
• CRISPR-Cas9