The genetic and endoplasmic reticulum-mediated molecular mechanisms of primary open-angle glaucoma

Abstract

Glaucoma is a heterogenous, chronic, progressive group of eye diseases, which results in irreversible loss of vision. There are several types of glaucoma, whereas the primary open-angle glaucoma (POAG) constitutes the most common type of glaucoma, accounting for three-quarters of all glaucoma cases. The pathological mechanisms leading to POAG pathogenesis are multifactorial and still poorly understood, but it is commonly known that significantly elevated intraocular pressure (IOP) plays a crucial role in POAG pathogenesis. Besides, genetic predisposition and aggregation of abrogated proteins within the endoplasmic reticulum (ER) lumen and subsequent activation of the protein kinase RNA-like endoplasmic reticulum kinase (PERK)-dependent unfolded protein response (UPR) signaling pathway may also constitute important factors for POAG pathogenesis at the molecular level. Glaucoma is commonly known as a ‘silent thief of sight’, as it remains asymptomatic until later stages, and thus its diagnosis is frequently delayed. Thereby, detailed knowledge about the glaucoma pathophysiology is necessary to develop both biochemical and genetic tests to improve its early diagnosis as well as develop a novel, ground-breaking treatment strategy, as currently used medical therapies against glaucoma are limited and may evoke numerous adverse side-effects in patients.