Regional pathology in glaucoma--an overlooked link to neuroprotective strategies.

Primary open-angle glaucoma (POAG) is the second commonest cause of blindness in the world. It is a neurodegenerative disease characterized by retinal ganglion cell loss. The molecular mechanism leading to glaucoma damage is unclear. Understanding the pathways that favor neuronal survival plus those that predispose to neuronal demise in POAG may have direct implications for other neurodegenerative diseases. POAG is a heterogeneous disease. A small subset of POAG patients develop damage in a highly focal form with a discrete sector of the optic nerve manifesting well delineated neuronal loss. It is hypothesized that this pattern of nerve loss indicates the optic nerve is not molecularly homogeneous. Genetic analysis of patients with isolated focal forms of POAG may enable new genes to be identified in glaucoma. Finding the responsible genes in POAG is a critical first step. The potential implications are earlier disease detection with resultant optimized visual preservation. Future treatment options could develop that include altered gene regulation, gene silencing or introducing repair genes. Determining the molecular causes for regional neuronal susceptibility could lead to identification of pathways underlying disease and ultimately effective patient-specific neuroprotective strategies.