allopurinol and Retinitis

We assessed the suppressive effect of a combination of cyclosporin (an immunosuppressive agent) and allopurinol (a xanthine oxidase inhibitor and radical scavenger) on experimental autoimmune uveoretinitis (EAU) in Lewis rats, induced by interphotoreceptor retinoid-binding protein (IRBP).. After the immunization of Lewis rats with 30 micrograms of IRBP. We administrated cyclosporin and/or allopurinol to the IRBP-immunized Lewis rats. We observed the incidence and the severity of EAU. Histological, immunological, and biochemical examinations were performal 13 days after the immunization. The suppressive effect of these drugs in vitro on the production of free radicals derived from polymorphonuclear leukocytes.. The incidence of EAU was suppressed by 50% at 13 days after immunization, and in terms of clinical and histological findings, inflammatory reaction was more inhibited by the combination of these drugs than by either cyclosporin or allopurinol alone. Lymphocyte proliferation assay against IRBP was significantly inhibited by the combination of drugs. No adverse systemic effects were identified. Cyclosporin and allopurinol inhibited radical production both separately and in combination.. This suggests that suppression of EAU is based not only on inhibited cell-mediated immunity but also on inhibited production of free radicals derived from polymorphonuclear leukocytes.

Topics: Allopurinol; Animals; Autoimmune Diseases; Cyclosporine; Free Radical Scavengers; Immunosuppressive Agents; Male; Rats; Rats, Inbred Lew; Retinitis; Uveitis; Xanthine Oxidase

Intravitreal injection of a superoxide-generating reaction mixture of xanthine oxidase and xanthine, either with or without rabbit plasma, was shown to be a mediator of an intense uveal and retinal inflammation in pigmented and albino rabbits. Controls of heat-inactivated xanthine oxidase with or without rabbit plasma, or plasma by itself, was without effect on ocular tissues. Xanthine alone as a control exhibited little or no inflammatory response. Controls of active xanthine oxidase by itself, or with rabbit plasma, produced a very strong inflammatory response that may represent enzymic reaction with endogenous xanthine. When the superoxide generating reaction mixture was given intravitreally the reaction began in the anterior segment within 16 hours and reached its peak after 2 days. The response in the posterior segment was delayed and did not become evident until after at least 24 hours, and may be due to the close proximity of the anterior chamber to the ciliary processes where cellular exudates first appear. Anterior segment uveitis began to recede after 4 days but posterior segment inflammation persisted beyond 6 days, and in many instances, led to retinitis, and retinal detachment. Superoxide dismutase was effectively used in vitro to quench superoxide in the reaction mixture but it did not prevent inflammatory reactions in vivo because it was found to possess strong toxic qualities of its own in ocular tissues. Other free radicals of oxygen, as well as hydrogen peroxide, can develop with the breakdown of superoxide, and cause tissue damage. A known ability of superoxide to convert a plasma precursor into a factor chemotactic for neutrophils may also cause superoxide production in situ by accumulating neutrophils. Because phagocytes are potential sources of superoxide, this study provides a good experimental model for studying the influence of oxygen free radicals in ocular inflammatory disease.

Topics: Animals; Female; Free Radicals; Male; Rabbits; Retinitis; Superoxides; Uveitis; Xanthine; Xanthine Oxidase; Xanthines