title: Amelioration of experimental autoimmune uveoretinitis by aldose reductase inhibition in Lewis rats.
abstract: OBJECTIVE
  Recently, the authors showed that the inhibition of aldose reductase (AR) prevents bacterial endotoxin-induced uveitis in rats. They have now investigated the efficacy of AR inhibitors in the prevention of experimental autoimmune-induced uveitis (EAU) in rats.
  
  
  METHODS
  Lewis rats were immunized with bovine interphotoreceptor retinoid-binding peptide (IRBP) to develop EAU. Two or 8 days after immunization, the rats started receiving the AR inhibitor fidarestat (7 mg/kg/d; intraperitoneally). They were killed when the disease was at its peak; aqueous humor (AqH) was collected from one eye, and the other eye of each rat was used for histologic studies. The protein concentration and the levels of inflammatory markers were determined in AqH. Immunohistochemical analysis of eye sections was performed to determine the expression of inflammatory markers. The effect of AR inhibition on immune response was investigated in isolated T lymphocytes.
  
  
  RESULTS
  Immunization of rats by IRBP peptide resulted in a significant infiltration of leukocytes in the posterior and the anterior chambers of the eye. Further, EAU caused an increase in the concentration of proteins, inflammatory cytokines, and chemokines in AqH, and the expression of inflammatory markers such as inducible-nitric oxide synthase and cycloxygenase-2 in the rat eye ciliary bodies and retina. Treatment with fidarestat significantly prevented the EAU-induced ocular inflammatory changes. AR inhibition also prevented the proliferation of spleen-derived T cells isolated from EAU rats in response to the IRBP antigen.
  
  
  CONCLUSIONS
  These results suggest that AR could be a novel mediator of bovine IRBP-induced uveitis in rats.
authors: Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas 77555, USA.
authors: Umesh C S
authors: UC
authors: Yadav
authors: Mohammad
authors: M
authors: Shoeb
authors: Satish K
authors: SK
authors: Srivastava
authors: Kota V
authors: KV
authors: Ramana
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005136:Eye Proteins; D019084:Fluorescent Antibody Technique, Indirect; D048289:Imidazolidines / Q000494:pharmacology*; D008213:Lymphocyte Activation; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D012173:Retinitis / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D012177:Retinol-Binding Proteins; D013601:T-Lymphocytes / Q000276:immunology; D014605:Uveitis / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D000099214:Retinol-Binding Proteins, Interstitial
chemical_list: D000449:Aldehyde Reductase; D051546:Cyclooxygenase 2; D016207:Cytokines; D015232:Dinoprostone; D004791:Enzyme Inhibitors; D005136:Eye Proteins; D048289:Imidazolidines; D052247:Nitric Oxide Synthase Type II; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial; C077139:fidarestat; C496318:Nos2 protein, rat