Effect of mycophenolate mofetil, cyclosporin A, and both in combination in a murine corneal graft rejection model

Abstract

AIMS: To compare the effectiveness of mycophenolate mofetil (MMF), cyclosporin A (CSA), and both in combination, in preventing rejection following corneal transplantations. METHODS: Rats of the inbred strains Brown Norway and Lewis were used as donors and recipients respectively. MMF was administered orally in both monotherapy and combination therapy for 14 days in a dosage of 40 mg/kg body weight, and CSA was administered, likewise for 14 days, in an intramuscular dosage of 10 mg/kg body weight. The transplants were examined every third day by slit lamp microscopy. Every transplant was subjected to histological or immunohistological evaluation. RESULTS: The average transplant survival rate in the allogenic strain combination was 7.9 days (SEM 1.1). Monotherapy with MMF led to a statistically significant prolongation of transplant survival to 11.6 days (SEM 0.9, p < 0.05). Monotherapy with CSA delayed transplant rejection statistically significantly longer than MMF (21 days, 0.0, p < 0.05). The combination therapy with CSA and MMF was statistically significantly superior to the monotherapy with MMF (22.3 days, 0.5, p < 0.05). The combination therapy prolonged transplant survival compared with the CSA monotherapy, albeit not to a statistically significant extent. CONCLUSIONS: In this study we were able to prove the immunosuppressive effect of oral MMF on acute rejection following corneal transplantation. Double drug therapy with CSA and MMF conferred a marginal benefit without a higher incidence of complications related to drug toxicity or overimmunosuppression.