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2001 Ocular Microbiology and Immunology Group, Abstract 17

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Reduction of Corneal Allorejection Mediated by Alpha-Melanocyte Stimulating Hormone Treatment
P. Hamrah, Z. Haskova, Q. Zhang, A.W. Taylor, B. Ksander and R. Dana
Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston MA
Purpose: To determine the possible role of a-MSH on orthotopic corneal allograft survival and the mechanisms by which it may influence graft outcome.

Methods: Orthotopic corneal allograft transplantation was performed with different strains of mice. Recipients either received a sham injection or were treated with 1.2 µg subconjunctival injections of a-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. Allospecific delayed type hypersensitivity (DTH) was compared among the groups 3 weeks post transplantation. Additionally, ocular gene expression of select inflammatory cytokines was evaluated at different time points by the ribonuclease protection assay.

Results: Corneal allografts in a-MSH-treated recipients showed an increase in graft survival as compared to untreated hosts. Over 70% of allografts in a-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 a-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 a-MSH treated mice as compared to untreated recipients.

Conclusion: We provide for the first time, in vivo evidence that treatment with the neuropeptide a-MSH reduces allorejection of corneal transplants.

This study was supported in part by Alcon Laboratories, INC.

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