INCREASED NITRIC-OXIDE PRODUCTION IN ENDOTOXIN-INDUCED UVEITIS - REDUCTION OF UVEITIS BY AN INHIBITOR OF NITRIC-OXIDE SYNTHASE

Nitric oxide (NO) has been implicated in the pathogenesis of several i nflammatory diseases. In the present study, we investigated the potent ial role of NO in an ocular model of inflammation, endotoxin-induced u veitis (EIU), in Lewis rats. Injection of LPS in one footpad induces s evere uveitis after 16 h, which is accompanied by an increase of NO in the aqueous and vitreous humors, as evaluated by nitrite assay. Rever se transcriptase-PCR experiments reveal a large increase of inducible NO synthase (iNOS) mRNA in the iris/ciliary body, from 2 to 24 h after LPS treatment. In the retina, maximal increase of iNOS mRNA was detec ted 16 h after LPS treatment. Two i.p, injections of the NOS inhibitor , N-G-nitro-L-arginine methyl ester (L-NAME), which inhibits nitrite r elease in the aqueous and vitreous humors, profoundly reduce clinical and histologic inflammation in EIU rats. These results implicate the N O pathway in the pathogenesis of EIU and demonstrate the possibility o f modulating this inflammatory disease by injection of a NOS inhibitor .