Purpose: Investigated the effect of N-3-aminomethylbenzylacetamidine (1400 W), a highly selective inhibitor of inducible nitric oxide synthase (iNOS), on the effector phase of EAU.
Methods: Sixteen Lewis rats were sensitized with bovine retinal S-antigen; ten of them injected subcutaneously with 1400 W (20 mg/kg) three times a day, from day 11 through day 13 following the injection of S-antigen. Five of the ten rats were also injected intraperitoneally with polyethylene-glycol-modified superoxide dismutase (SOD 1000 IU) twice a day from day 7 through day 13. Six rats received intraperitoneal and/or subcutaneous injections of normal saline from day 7 through day 13. The eyes were enucleated on day 14. The intensity of the inflammatory lesion was assessed by a histological score. The thickness of the choroidal and photoreceptor layers was measured.
Results: The histological score was higher in the 1400 W-treated rats (26 +/- 2.1) than in the saline- (20.5 +/- 8; p < 0.0001) or 1400 W/SOD-treated rats (20.5 +/- 4.9; p < 0.005). The choroid was thicker in the 1400 W-treated rats (60.7 +/- 16.8 microm) than in the saline- (19.2 +/- 9.4 microm, p < 0.0005) or the 1400 W/SOD-treated rats (29.6 +/- 19.3 microm, p < 0.05). The photoreceptor layer was thinner in the 1400 W-treated rats (8.4 +/- 32.1 microm) than in the saline- (40 +/- 26.7 microm; p < 0.05) or 1400 W/SOD-treated rats (60.8 +/- 38.1 microm; p < 0.05).
Conclusions: The data suggests that 1400 W exacerbates choroidal inflammation and photoreceptor damage at the effector phase of S-antigen-induced uveitis. This implies that iNOS expressed in the outer retina may have a protective role in EAU.