THE ROLE OF NITRIC-OXIDE IN UVEITIS

Objective: To evaluate the possible role played by nitric oxide in the pathogenesis of uveitis. Methods: Uveitis was induced in rats with subcutaneous lipopolysaccharide. Lipopolysaccharide stimulates nitric oxide production from L-arginine. The animals were treated with N-G-nitro-L-arginine methyl ester, an L-arginine analogue acting as a specific inhibitor of nitric oxide synthesis. Ocular inflammation was evaluated by measuring protein concentration and leukocyte number in the aqueous humor of one eye, and by histopathologic examination of the contralateral eye. Results: Aqueous humor protein levels were reduced 73% to 82% and cellular infiltration was almost abrogated in N-G-nitro-L-arginine methyl ester-treated rats compared with controls. The histopathologic examination also showed a similar inhibition of uveal tissue inflammation in treated rats. Conclusion: By inhibiting nitric oxide synthesis, N-G-nitro-L-arginine methyl ester inhibits the induction of endotoxin-induced uveitis in the rat. This observation demonstrates that nitric oxide is an important mediator of anterior uveitis in this model system and suggests that nitric oxide may also be implicated in human uveitis.