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[1]References
- Free radical mediated photoreceptor damage in uveitis. Rao, N.A., Wu, G.S. Progress in retinal and eye research. (2000) [Pubmed]
Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenesOpen Access LicencePrivacy PolicyTerms of Useapsburg
