Cellular Pathways and Therapeutic Approaches to Neurodegeneration of Retinal Ganglion Cells in Glaucoma

Glaucoma is one of the main causes of irreversible blindness and characterized by a slow-progressive degeneration of retinal ganglion cells (RGCs) bodies mainly living in GCL, as well as their axons. Although elevated IOP is a primary risk factor, RGC degeneration entails numerous pathological processes such as oxidative stress, mitochondrial dysfunction, glutamate excitotoxicity. It seems clear that by simply lowering IOP with traditional therapies is not enough to prevent the progression of glaucoma because there are people who continue losing their RVF despite having a "normal" IOP. Hence, this review investigates the cellular pathways responsible for RGC loss and examines current or prospective therapeutic strategies to prevent blindness due to neurodegeneration. The aim of Neuroprotection includes targeting excitotoxicity by modulating calcium homeostasis with NMDA receptor antagonists and Calcium channel blockers. Coenzyme Q10 and α-lipoic acid are antioxidant agents that support mitochondrial function and protect against oxidative stress. Anti-inflammatory therapies attack chronic glial activation which further decreases the emission of pro inflammatory cytokines amplifying RGC degeneration. Furthermore, the neurotrophic factors brain-derived growth factor (BDNF) and ciliary ganglionoma associated protein-1 peptide (CDNAp/ CNTF; National Institute of Health R28), which are also necessary for survival or nerve fiber regrowth from mature adult retinal neurons have been characterized. Furthermore, gene therapy and stem cell transplantation as promising approaches can prevent apoptosis of RGCs and restore retinal function. Nonetheless, hurdles still exist with respect to maximizing drug delivery and compliance amongst patients alongside creating individualized therapies. This necessitates future research on the combination of IOP-lowering therapies with neuroprotective strategies or regeneration to target all mechanisms in glaucoma.