Nitroxide stable radical suppresses autoimmune uveitis in rats

Free radicals have been implicated in the pathogenesis of experimental auto immune uveoretinitis (EAU). Nitroxides are stable radicals with a superoxid e-dismutase-mimicking activity, which exert an anti-inflammatory effect in various animal models of oxidative damage and inflammation, such as experim ental colitis and head trauma. We examined the use of the SOD mimic nitroxi de 4-hydroxy-2,2,6,6,-tetramethylpiperidine-1-N-oxyl (TPL) to suppress EAU. Adult male Lewis rats were immunized with 125 mu g/rat synthetic human ret inal S-Ag, emulsified with Freund's adjuvant. Intravenous pertussis toxin w as simultaneously injected. Beginning on Day 6, rats were injected with a d aily intraperitoneal dose of 35, 175 or 350 mu mol/rat of the nitroxide TPL . Control rats received intraperitoneal normal saline. The animals were exa mined daily, and on the 19th day the eyes were enucleated. Aqueous protein concentrations and retinal lipid peroxidation product levels (ketodienes an d conjugated dienes) were determined. Histological sections were stained an d examined microscopically. TPL was found to penetrate the aqueous humor re adily. Beginning on day 12, rats developed a severe pan-uveitis. Rats in th e treatment group had a lower mean clinical and histological score than tha t of controls. Levels of aqueous humor protein, retinal conjugated diens an d ketodiens were all significantly lower in the treatment group. This effec t was more pronounced with the lower TPL concentration. We conclude that TP L reduces clinical, biochemical and histopathological severity of S-Ag indu ced EAU in Lewis rats. This effect is probably mediated by removal of super oxide radicals, but other mechanisms may also be involved. (C) 1999 Elsevie r Science Inc.