Role of Peroxynitrite in Photoreceptor Damage in Experimental Uveitis

Abstract

With inflammation, as in uveitis, the phagocytes undergo respiratory burst resulting in the release of a variety of microbicidal oxygen metabolites. The most important primary species of these metabolites are superoxide and hydrogen peroxide, both of which are potentially injurious to surrounding tissues. The superoxide-mediated toxicity in vivo, however, has been difficult to demonstrate because of the low chemical reactivity of the superoxide anion. It was presumed that the cytotoxicity was exerted through formation of highly reactive hydroxyl radicals via the interaction of superoxide with hydrogen peroxide (Weiss and LoBuglio 1982); but the current understanding of cytotoxicity via the reactivity of hydroxyl radicals does not always offer a satisfactory explanation for the experimental results generated (Babbs and Griffin 1989). Therefore, it appears that there must be another pathway to account for the toxicity of superoxide in inflammatory conditions, including the reaction of superoxide with another abundantly generated species, nitric oxide, to form the potent oxidant peroxynitrite. The reaction between superoxide and nitric oxide proceeds at a nearly diffusion-limited rate. The product generated by this reaction is capable of abstracting hydrogen atoms from lipids and nitrating aromatic amino acid residues of cellular macromolecules.