Person:

Ksander, Bruce

Background

Corneal grafting is by far the most common form of transplantation. Many grafts suffer from immune rejection and current therapies are associated with many side effects, requiring more effective and safe therapies. Alpha–melanocyte stimulating hormone (α–MSH) is a neuropeptide that suppresses host inflammatory defense mechanisms. The purpose of this study was to determine the role of local therapy with α-MSH on corneal allograft survival, and the mechanisms by which it may influence graft outcome.

Methods

Orthotopic corneal transplantation was performed, with recipients receiving subconjunctival α-MSH or sham injections twice weekly. Grafts were followed for 70 days and graft inflammation/opacification was compared between the two groups in a masked fashion. Graft infiltration and ocular gene expression of select inflammatory cytokines was evaluated at different timepoints. Additionally, allospecific delayed type hypersensitivity (DTH) was compared among the groups 3 weeks post transplantation.

Results

Results showed a significant increase in corneal graft survival in α-MSH-treated recipients as compared to controls. While 75% of allografts in α-MSH-treated hosts survived at 70 days, 43% survived in controls (p=0.04). Graft infiltration studies demonstrated a significant decrease in the number of mononuclear and polymorphonuclear cells in α-MSH-treated mice as compared to controls at days 7 and 14 after transplantation. Further, allospecific DTH and gene expression of interferon-γ and interleukin-2 showed a significantly reduced expression in α-MSH-treated mice as compared to controls.

Conclusions

In this study, we provide for the first time, in vivo evidence that treatment with local α-MSH may significantly reduce allorejection of orthotopic transplants.