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P Hamrah, Z Haskova, Q Zhang, AW Taylor, B Ksander, MR Dana; Treatment With Alpha-MSH Reduces Corneal Allorejection . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2961.
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Purpose:α-Melanocyte stimulating hormone (α-MSH) is a proopiomelanocortin-derived neuropeptide that suppresses mammalian host inflammatory defense mechanisms. The purpose of this study was to determine the possible role of α-MSH on orthotopic corneal allograft survival and the mechanisms by which it may influence graft outcome. Methods:Orthotopic corneal transplantation was performed using corneal buttons of C56BL/6 mice grafted into BALB/c recipients. Recipients either received a sham injection or were treated with 2.0 µg subconjunctival injections of α-MSH twice weekly. Grafts were followed for 70 days and graft inflammation/opacification was compared between the two groups in a masked fashion. Additionally, graft infiltration was determined in both groups at days 7 and 14. Ocular gene expression of select inflammatory cytokines was evaluated at different timepoints by the ribonuclease protection assay. Additionally, allospecific delayed type hypersensitivity (DTH) was compared among the groups 3 weeks post transplantation. Results:Corneal allografts in α-MSH-treated recipients showed an increase in graft survival as compared to untreated hosts. Over 70% of allografts in α-MSH treated hosts survived at 70 days, compared to less than 50% in the untreated group. Graft infiltration by mononuclear and polymorphonuclear (PMN) cells was significantly decreased in α-MSH treated mice compared to untreated hosts (P<0.05). Moreover, DTH results and cytokine expression (including Interferon-g and Interleukin-2) were significantly reduced in α-MSH treated mice as compared to untreated recipients. Conclusion:We provide, for the first time, in vivo evidence that treatment with α-MSH may significantly reduce allorejection of corneal transplants.
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