title: S-nitrosoglutathione prevents interphotoreceptor retinoid-binding protein (IRBP(161-180))-induced experimental autoimmune uveitis.
abstract: OBJECTIVE
  Experimental autoimmune uveitis (EAU), an animal model of human uveitis, is an organ-specific autoimmune disease mediated by various inflammatory cytokines. In particular, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and interferon (IFN)-gamma are known to play a role in its pathogenesis. S-nitrosothiol S-nitrosoglutathione (GSNO), a slow nitric oxide (NO) donor, was reported to have beneficial effects in inflammatory disease in ischemia-reperfusion injury. The efficacy of GSNO treatment on interphotoreceptor retinoid-binding protein (IRBP)-induced EAU was investigated, using functional, histologic, and immunologic readouts.
  
  
  METHODS
  Mice were immunized with a single injection of IRBP(161180) peptide to induce EAU, followed by a daily treatment with GSNO (1 mg/kg). Electroretinogram (ERG) analysis, histopathology, and immunologic responses to IRBP were analyzed. The effects of GSNO treatment on the antigen-specific T-cell recall responses and their cytokine production were determined.
  
  
  RESULTS
  A single immunization of IRBP(161180) peptide led to significant structural damage of the retina and concomitant elimination of ERGs. Daily oral GSNO treatment from days 1-14 following immunization was found to be effective against IRBP-induced EAU. Histopathologic and ERG analysis both demonstrated significant retinal protection in GSNO-treated mice. The GSNO treatment of EAU animals significantly attenuated the levels of TNF-alpha, IL-1beta, IFN-gamma, and IL-10 in retinas, as measured by quantitative real-time polymerase chain reaction analysis. The splenocytes isolated from EAU- and GSNO-treated mice had lower antigen-specific T-cell proliferation in response to IRBP protein, and their cytokine production was inhibited.
  
  
  CONCLUSIONS
  The oral administration of GSNO significantly suppressed the levels of inflammatory mediators in the retinas of EAU mice. This suppression was associated with the maintenance of normal retinal histology and function. These results clearly demonstrated the therapeutic potential of GSNO in EAU, and provide new insights for the treatment of human uveitis.
authors.affiliation: Department of Pediatrics, Medical University of South Carolina, Charleston, SC 29425, USA.
authors.forename: Ehtishamul
authors.initials: E
authors.lastname: Haq
authors.forename: Baerbel
authors.initials: B
authors.lastname: Rohrer
authors.forename: Narender
authors.initials: N
authors.lastname: Nath
authors.forename: Craig E
authors.initials: CE
authors.lastname: Crosson
authors.forename: Inderjit
authors.initials: I
authors.lastname: Singh
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control*; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004596:Electroretinography; D005136:Eye Proteins; D008297:Male; D051379:Mice; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D010786:Photoreceptor Cells; D016133:Polymerase Chain Reaction; D012160:Retina / Q000187:drug effects / Q000503:physiopathology; D012177:Retinol-Binding Proteins; D026422:S-Nitrosoglutathione / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D014605:Uveitis / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control*; D000099214:Retinol-Binding Proteins, Interstitial
chemical_list: D016207:Cytokines; D005136:Eye Proteins; D020030:Nitric Oxide Donors; D012177:Retinol-Binding Proteins; D026422:S-Nitrosoglutathione; D000099214:Retinol-Binding Proteins, Interstitial