Oxidative photoreceptor cell damage in autoimmune uveitis

Angeline M Nguyen,Narsing A Rao

doi:10.1007/s12348-010-0007-5

Abstract

Uveitis comprises an extensive array of intraocular inflammatory diseases and often results in irreversible visual loss. Experimental autoimmune uveitis (EAU) is an animal model used to study human uveitis. Both innate and adaptive immune responses are known to mediate retinal damage in EAU. The innate immune response occurs first with activation of toll-like receptors which upregulate inflammatory cytokines, leading to oxidative stress; subsequently, the adaptive immune response results in inflammatory cytokine upregulation and mitochondrial oxidative stress. In early EAU, mitochondrial DNA is damaged before inflammatory cellular infiltration and alters mitochondrial protein levels and the functions of mitochondria in AU. Our recent study confirms the importance of TLR4 in the generation of inflammatory cytokines, initiation of oxidative DNA damage, and induction of mitochondrial oxidative stress. Like EAU, sympathetic ophthalmia also results in photoreceptor mitochondrial oxidative damage. Agents that prevent mitochondrial oxidative stress and photoreceptor apoptosis may help prevent retinal damage and preserve vision in uveitis.

Highlights

Uveitis is one of the major causes of blindness due primarily to retinal tissue damage, especially retinal photoreceptorA
Both the adaptive and innate immune responses mediate retinal damage; the innate immune response occurs first with tolllike receptors upregulating inflammatory cytokines which leads to the induction of oxidative stress; the adaptive immune response occurs on a cellular level, and results in inflammatory cytokine upregulation and oxidative stress (Fig. 2)
Other proteins with altered expression due to early Experimental autoimmune uveitis (EAU) were calretinin, mitochondrial aspartate aminotransferase, and malate dehydrogenase; we found decreased levels of calretinin, increased levels of mitochondrial aspartate aminotransferase, and decreased levels of malate dehydrogenase when compared to controls

Summary

Introduction

Uveitis is one of the major causes of blindness due primarily to retinal tissue damage, especially retinal photoreceptor. Contrary to earlier observations, later studies revealed that during the early phase of EAU (postimmunization day 5) retinal ONOO− initiated damage occurred before there was any histologic or immunohistochemical evidence of macrophage infiltration or migration of retinal microglia [6, 15]. These findings suggest that the innate immune response may play a role in inducing peroxynitrite-mediated oxidative stress during the early phase of EAU. This review explores evidence for the development of mitochondrial oxidative stress from innate and adaptive immune effector processes of EAU and the stress-related retinal damage during autoimmune uveitis

Photoreceptor mitochondrial oxidative stress

Photoreceptor oxidative damage in sympathetic ophthalmia

Conclusion