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Yoko Okunuki, Yoshihiko Usui, Takeshi Kezuka, Hayate Nakagawa, Ma Juan, Hiroshi Goto; Suppression Of Experimental Autoimmune Uveoretinitis By Agonist Of Peroxisome Proliferator Activated Receptor-gamma. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2273.
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Peroxisome proliferator activated receptor (PPAR)-gamma is a member of a ligand-activated nuclear receptor superfamily and used as oral antihyperglycemic agents for the therapy of non-insulin-dependent diabetes mellitus. Recent studies have reported that PPAR-gamma agonists have a potent anti-inflammatory effect. In this study, we report the effect of one of the PPAR-gamma agonists, piglitazone, on the suppression of experimental autoimmune uveitis (EAU).
Female C57BL/6 mice were immunized with interphotoreceptor retinoid binding protein derived peptide 1-20. Pioglitazone (10 mg/kg or 25 mg/kg) or vehicle was administrated intraperitoneally from day -1 (whole phase) or from day 8 (effecter phase) to the day before sacrifice. On day 21 after immunization, severity of EAU was assessed clinically and histopathologically. Activation of draining lymph nodes (LN) was assessed by means of fluorescence intensity (MFI) of CD4+CD44high T cells and CD4+CD62Lhigh T cells using a flow cytometer. Intraocular concentrations of inflammatory factors (IFN-gamma, TNF-alpha, IL-6, IL-10, IL-12p70, and MCP-1) were assessed on day 14 after immunization.
EAU was clinically (p<0.05) and histopathologically (p<0.05) suppressed by administration of both whole phase and effector phase administrations of pioglitazone (25 mg/kg). In effector phase treatment of pioglitaoze, numbers of LN cells were lower (p<0.001) and MFI of CD4+CD62high T cells were higher (p<0.001) in pioglitazone treated mice. In whole phase treatment of pioglitazone, intraocular expression of MCP-1, IL-6, and TNF-alpha were lower (p<0.05) in pioglitazone treated mice evaluated on day 14 after immunization.
Systemic administration of PPAR-gamma agonist, pioglitazone, significantly suppressed EAU by inhibiting activation of draining LN cells and the production of inflammatory chemokines in the eye. These results indicate that pioglitazone could be one of the new therapeutic regimens for endogenous uveitis.
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