Free radical mediated photoreceptor damage in uveitis.
Uveitis is a major cause of blindness, with the visual loss that occurs being due primarily to retinal tissue damage. The tissue damage is mediated mainly by phagocytic inflammatory cells, such as macrophages, by the release of various proteolytic enzymes, arachidonic acid metabolites, cytokines and free radicals. The latter are found to be potent cytotoxic agents that readily cause tissue damage by peroxidation of lipid cell membranes. Recent studies of experimental uveitis indicate that other potent oxidants are generated in uveitis by macrophages. One of these is ONOO-, which is formed from *NO and O(-)2. The macrophages generate *NO preferentially in the outer retina following iNOS expression. In these phagocytes, outer retinal proteins, especially arrestin, are found to be potent iNOS inducers. Current studies of RPE show that these cells protect the retina from ONOO- mediated damage in uveitis by releasing a novel protein called retinal pigment epithelial protective protein. This protein is found to suppress O(-)2 and *NO generation by the phagocytes, in both in vitro and in vivo uveitis models. The protective protein expression is restricted to RPE, its suppressive effect is a result of the inhibition of the phosphorylation of cytosolic proteins, p47-phox, required for the assembly of NADPH and activation of NFkappaB, which are required for generation of 0(-)2 and expression of iNOS respectively. Either pharmacologically or chemically, up-regulation of RPP generation could help in preventing retinal degeneration in uveitis or other degenerative dis
Rao
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Doheny Eye Institute and Department of Ophthalmology and Pathology, University of Southern California, Los Angeles 90033-1088, USA. inavarro@hsc.usc.edu
Wu
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D000818:Animals; D005544:Forecasting; D005609:Free Radicals / Q000378:metabolism*; D006801:Humans; D015227:Lipid Peroxidation / Q000502:physiology*; D010786:Photoreceptor Cells / Q000473:pathology*; D010857:Pigment Epithelium of Eye / Q000502:physiology*; D014605:Uveitis / Q000473:pathology*
D005609:Free Radicals