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D.J. Biros, A.W. Taylor; Suppression of Experimental Autoimmune Uveitis Using a Plasmid Encoding the Ocular Immunosuppressive Cytokine Alpha-Melanocyte Stimulating Hormone . Invest. Ophthalmol. Vis. Sci. 2003;44(13):4307.
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Purpose: Recently we have reported that intravenous injections of the ocular immunosuppressive cytokine alpha-melanocyte stimulating hormone (α-MSH) into mice immunized for experimental autoimmune uveitis (EAU) suppress the incidence and severity of EAU. We have also demonstrated that α-MSH induces the activation of regulatory T cells (Treg). Further these Treg cells when adoptively transferred to EAU-susceptible mice suppress the incidence and severity of EAU. It is not known, however, if local delivery of α-MSH to the ocular environment can also suppress EAU or if the immunosuppressive effects can be sustained in the ocular microenvironment. Therefore, to study the effects of local α-MSH delivery to the eyes of mice with EAU we examined both direct α-MSH peptide injections and injections of a gene encoding for α-MSH for their ability to suppress EAU. Methods: 6 week old B10.RIII mice were immunized subcutaneously with 50 µg of IRBPp (161-180) emulsified with Complete Freunds Adjuvant. The uveoretinitis was monitored clinically every 3 days via direct ophthalmoscopy. Inflammation was graded on a scale from 1 to 5. On days 6 and 9 post-immunization mice received into the subconjunctival space of each eye 5µg of either a plasmid containing the gene encoding for α-MSH, an empty plasmid, or the α-MSH peptide. The difference between 2 clinical scores was statistically analyzed by the nonparametric Mann-Whitney test for comparison of 2 independent populations. Differences in the incidence of EAU were evaluated statistically by the Fisher exact test. Statistical differences were significant when P < 0.05. Results: Mouse eyes injected with the plasmid encoding for α-MSH showed significant suppression of EAU (30% incidence) by contrast to eyes that received either saline (78% incidence) or empty plasmid (86% incidence). Eyes receiving α-MSH peptide also showed diminished severity and incidence of EAU when compared to control eyes. Conclusions: Both the plasmid containing the gene encoding for α-MSH and the α-MSH peptide suppressed the severity and incidence of EAU over empty plasmid or saline injections. This demonstrates that the reintroduction of an ocular immunosuppressive cytokine during uveitis suppresses the autoimmune disease.
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