Highly selective inhibitor of inducible nitric oxide synthase enhances S-antigen-induced uveitis.
OBJECTIVE
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.
Charlotte
Frederic
F
Department of Pathology, Pitie-Salpetriere Hospital, Paris, France.
Ito
Shinji
S
Wu
Guey
G
Kimoto
Takashi
T
Rao
Narsing
N
D000578:Amidines / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D019393:Arrestin / Q000276:immunology*; D001596:Benzylamines / Q000008:administration & dosage / Q000494:pharmacology*; D002829:Choroid / Q000187:drug effects / Q000473:pathology; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052247:Nitric Oxide Synthase Type II; D010786:Photoreceptor Cells / Q000187:drug effects / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D013482:Superoxide Dismutase / Q000008:administration & dosage / Q000494:pharmacology; D014605:Uveitis / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*
D000578:Amidines; D019393:Arrestin; D001596:Benzylamines; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; C104820:N-(3-(aminomethyl)benzyl)acetamidine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D013482:Superoxide Dismutase