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D.J. Biros, N. Kitaichi, A.W. Taylor; The Melanocortin 5 Receptor is Found in the Eye and is Integral to the Ocular Immunosuppressive Microenvironment . Invest. Ophthalmol. Vis. Sci. 2005;46(13):1044.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: The ocular neuropeptide alpha–melanocyte stimulating hormone (α–MSH) is a central mediator of regional ocular immunity. One of receptors to which α–MSH binds, the melanocortin 5 receptor (Mc5r), is the only known melanocortin receptor on CD4+ T cells. We have shown that through the MC5r, α–MSH mediates not only the suppression of interferon gamma (IFN–γ) production by T cells but also the induction of transforming growth factor–beta (TGF–ß)–producing CD25+ CD4+ regulatory T (Treg) cells. Therefore we ask if there is a role for the MC5r in ocular immunosuppression. Methods: We induced experimental autoimmune uveitis (EAU) in wild type (C57BL/6) and MC5r knockout (MC5r(–/–)) mice with subcutaneous injection of the immunodominant peptide of human interphotoreceptor retinoid binding protein amino acid 1–20 emulsified in Freund’s adjuvant followed by an intraperitoneal injection of pertussis toxin. We observed and scored the uveoretinal disease by direct ophthalmoscopic examination. The eyes were collected and fixed after clinical resolution of EAU (day 60) for histopathologic examination. As an additional control we collected healthy eyes from both WT and MC5r(–/–) mice. Some eyes received a plasmid encoding the gene for α–MSH prior to the peak of disease. We also stained fresh eye sections from healthy WT and MC5r(–/–) mice for MC5r using immunofluorescent antibodies. Results: WT and MC5r(–/–) mice had similar clinical duration and severity of EAU. Uveoretinal damage, however was much more severe in MC5r(–/–) mice than WT mice. Non–immunized eyes from MC5r(–/–) mice exhibit normal retinal structure. The α–MSH gene therapy suppressed EAU in the WT mice (p < 0.05) but not in the MC5r(–/–) mice. The WT eyes showed strong immunofluorescent signal for MC5r in discrete layers of the retina. Conclusions: Our results indicate that the MC5r is found in healthy ocular tissue and its expression is needed for effective α–MSH–mediated suppression of uveitis. The integrity of the ocular immunosuppressive microenvironment may in part depend on the expression of MC5r in the retina.
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