Current uveitis therapies are inadequate and have significant side effects. Recent research provides evidence that oxygen free radicals and oxidative damage are involved in experimental uveitis and other ocular inflammations. Experiments completed under the Phase I SBIR Grant indicate that certain NRTs are active in an endotoxin uveitis model. The PI proposes to extend this research to determine if NRTs can control ocular inflammation using two additional models of uveitis. Both are models of autoimmune uveitis, with one affecting primarily the anterior chamber of the eye (bovine melanin-protein) and one affecting the posterior segment of the eye (S-antigen). In human patients, the pathological damage to the retina and choroid in posterior uveitis can result in blindness. Both animal models are clinically relevant models of uveitis and closely mimic the human uveitis condition. Three candidate NRTs will be tested by the topical route in the bovine melanin-protein model of anterior uveitis. These candidate NRTs will also be evaluated by the systemic route in the S-antigen-induced model of posterior uveitis. If NRTs demonstrate efficacy in one or both of these models, we will proceed with the selection of an NRT for clinical development.
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