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

Br J Ophthalmol. 1998 Jun;82(6):700-3. doi: 10.1136/bjo.82.6.700.

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.

MeSH terms

  • Animals
  • Corneal Transplantation*
  • Cyclosporine / therapeutic use*
  • Drug Therapy, Combination
  • Graft Rejection / prevention & control*
  • Immunosuppressive Agents / therapeutic use*
  • Mycophenolic Acid / analogs & derivatives*
  • Mycophenolic Acid / therapeutic use
  • Rats
  • Rats, Inbred BN
  • Rats, Inbred Lew

Substances

  • Immunosuppressive Agents
  • Cyclosporine
  • Mycophenolic Acid