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 (alpha-MSH) is a neuropeptide that suppresses host inflammatory defense mechanisms. The purpose of this study was to determine the role of local therapy with alpha-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 alpha-MSH or sham injections twice weekly. Grafts were followed up 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 was compared among the groups 3 weeks posttransplantation. RESULTS: Results showed a significant increase in corneal graft survival in alpha-MSH-treated recipients compared with controls. Although 75% of allografts in alpha-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 alpha-MSH-treated mice compared with controls at days 7 and 14 after transplantation. Furthermore, allospecific delayed-type hypersensitivity and gene expression of interferon-gamma and interleukin-2 showed a significantly reduced expression in alpha-MSH-treated mice compared with controls. CONCLUSIONS: This study provides for the first time, in vivo evidence that treatment with local alpha-MSH may significantly reduce allorejection of orthotopic transplants.
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 (alpha-MSH) is a neuropeptide that suppresses host inflammatory defense mechanisms. The purpose of this study was to determine the role of local therapy with alpha-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 alpha-MSH or sham injections twice weekly. Grafts were followed up 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 was compared among the groups 3 weeks posttransplantation. RESULTS: Results showed a significant increase in corneal graft survival in alpha-MSH-treated recipients compared with controls. Although 75% of allografts in alpha-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 alpha-MSH-treated mice compared with controls at days 7 and 14 after transplantation. Furthermore, allospecific delayed-type hypersensitivity and gene expression of interferon-gamma and interleukin-2 showed a significantly reduced expression in alpha-MSH-treated mice compared with controls. CONCLUSIONS: This study provides for the first time, in vivo evidence that treatment with local alpha-MSH may significantly reduce allorejection of orthotopic transplants.
Authors: Stefano Gatti; Gualtiero Colombo; Roberto Buffa; Flavia Turcatti; Letizia Garofalo; Nadia Carboni; Luca Ferla; Luigi R Fassati; James M Lipton; Anna Catania Journal: Transplantation Date: 2002-12-27 Impact factor: 4.939
Authors: Lu Chen; Pedram Hamrah; Claus Cursiefen; Qiang Zhang; Bronislaw Pytowski; J Wayne Streilein; M Reza Dana Journal: Nat Med Date: 2004-07-04 Impact factor: 53.440
Authors: Zala Lužnik Marzidovšek; Tomas Blanco; Zhongmou Sun; Hamid Alemi; Gustavo Ortiz; Hayate Nakagawa; Sunil K Chauhan; Andrew W Taylor; Ula V Jurkunas; Jia Yin; Reza Dana Journal: Am J Pathol Date: 2021-11-11 Impact factor: 4.307
Authors: Takefumi Yamaguchi; Aslihan Turhan; Deshea L Harris; Kai Hu; Harald Prüss; Ulrich von Andrian; Pedram Hamrah Journal: PLoS One Date: 2013-08-14 Impact factor: 3.240