Neurodegeneration in retinal diseases and new strategies in its inhibition

Abstract

AbstractPurpose Recent studies showed the role of toll‐like receptors (e.g.TLR4) in the generation of inflammatory cytokines, initiation of oxidative DNA damage, and induction of mitochondrial oxidative stress.Methods Several retinal diseases result in photoreceptor mitochondrial oxidative damage. The oxidative‐stress‐induced nitration of photoreceptor mitochondrial proteins and peroxidation of membrane lipids led to activation and migration of microglia toward the photoreceptors. These observations suggest oxidative stress could be an initial pathologic event leading to amplification of inflammation inducing photoreceptor damage. Molecules that prevent mitochondrial oxidative stress and photoreceptor apoptosis may help prevent retinal damage and preserve vision in patients with different retinal disease.Results Several different agents were investigated to reduce the mitochondrial oxidative stress. The small heat shock protein alpha‐A crystallin prevents photoreceptor mitochondrial oxidative stress‐mediated apoptosis in inflammatory disease such an experimental autoimmune uveitis (EAU). Interestingly, only alpha‐A and not alpha‐B‐crystallin, a closely related small heat shock protein works, pointing to molecular specificity in the observed retinal protection. based on modulation of the systemic B and T cell immunity.Conclusion In the ischemic retinal diseases the neuroprotective role of neuroglobin has been shown. Neuroglobin overexpression plays a protective role against retinal ischemia reperfusion injury due to decreasing of mitochondrial oxidative stress‐mediated apoptosis.