The Role of Endogenous Neuroprotective Mechanisms in the Prevention of Retinal Ganglion Cells Degeneration

Abstract

Retinal neurons are not able to undergo spontaneous regeneration in response to damage. A variety of stressors, i.e., UV radiation, high temperature, ischemia, allergens, and others, induce reactive oxygen species production, resulting in consecutive alteration of stress-response gene expression and finally can lead to cell apoptosis. Neurons have developed their own endogenous cellular protective systems. Some of them are preventing cell death and others are allowing functional recovery after injury. The high efficiency of these mechanisms is crucial for cell survival. In this review we focus on the contribution of the most recently studied endogenous neuroprotective factors involved in retinal ganglion cell (RGC) survival, among which, neurotrophic factors and their signaling pathways, processes regulating the redox status, and different pathways regulating cell death are the most important. Additionally, we summarize currently ongoing clinical trials for therapies for RGC degeneration and optic neuropathies, including glaucoma. Knowledge of the endogenous cellular protective mechanisms may help in the development of effective therapies and potential novel therapeutic targets in order to achieve progress in the treatment of retinal and optic nerve diseases.

The effects of intravitreal H2S application on apoptosis in the retina and cornea in experimental glaucoma model

“…The significant role of Bax which is a pro‐apoptotic protein for glaucoma formation was reported in previous studies . Libby et al carried out a study on mice with DBA/2J Bax ablation and revealed that Bax was a significant factor in RGC death, that Bax ablation prevented apoptosis in RGC, and that Bax ablation decelerated axonal death even though there is no Bax‐associated apoptosis .…”

Computational Analysis of Clinical and Molecular Markers and New Theranostic Possibilities in Primary Open-Angle Glaucoma

“…As BDNF may trigger a wide variety of neutroprotective mechanisms, we may hypothesize that BDNF may benefit the glaucoma course by acting as anti-apoptotic, as well as anti-autophagic molecule, to strengthen cell survival. In this context, the fatty acid amide hydrolase inhibitors and endocannabinoid system were investigated as glaucoma neuroprotectans [72]. An interesting review [73] focused on endogenous neuroprotective factors involved in RGCs survival, covering new therapeutic strategies, as the ones suggested herein.…”

Neuroprotective Strategies for Retinal Ganglion Cell Degeneration: Current Status and Challenges Ahead

“…Neurotrophic factors generally include the neurotrophin family: NGF, BDNF, neurotrophin-3 (NT-3) and neurotrophin-4/5 (NT-4/5); the glial cell-line derived neurotrophic factor (GDNF) family: GDNF, neurturin (NRTN), artemin (ARTN), and persephin (PSPN); and CNTF [80,81]. It was reported that most of these neurotrophic factors, which can be produced by glial cells, increase RGC survival in different experimental models of injury [53,[82][83][84][85][86][87][88]. Neurotrophic factors bind to different receptors and transduce diverse intracellular signals.…”

“…It was reported that most of these neurotrophic factors, which can be produced by glial cells, increase RGC survival in different experimental models of injury [53,[82][83][84][85][86][87][88]. Neurotrophic factors bind to different receptors and transduce diverse intracellular signals.…”