Related Experiment Video
Updated: Oct 7, 2026
Murine Corneal Transplantation: A Model to Study the Most Common Form of Solid Organ Transplantation
Published on: November 17, 2014
Effect of mycophenolate mofetil, cyclosporin A, and both in combination in a murine corneal graft rejection model
A Reis1, T Reinhard, R Sundmacher
1Eye Clinic, Heinrich-Heine University, Duesseldorf, Germany.
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.
Insights
Mycophenolate mofetil (MMF) and cyclosporine A (CSA) both prevent corneal transplant rejection in rats. Combination therapy with MMF and CSA offered a slight survival benefit over CSA alone.
Area of Science:
- Immunology
- Ophthalmology
- Pharmacology
Background:
- Corneal transplantation is susceptible to immune rejection.
- Effective immunosuppression is crucial for graft survival.
Purpose of the Study:
- To evaluate mycophenolate mofetil (MMF) and cyclosporine A (CSA) monotherapy and combination therapy for preventing corneal transplant rejection.
- To compare the efficacy of MMF, CSA, and their combination in a rat model.
Main Methods:
- Allogeneic corneal transplantation was performed in Brown Norway to Lewis rats.
- Rats received oral MMF (40 mg/kg) or intramuscular CSA (10 mg/kg) daily for 14 days, or both.
- Transplant survival was monitored via slit lamp microscopy and histological evaluation.
Main Results:
- MMF monotherapy significantly prolonged graft survival to 11.6 days compared to controls (7.9 days).
- CSA monotherapy significantly extended survival to 21 days.
- Combination therapy (22.3 days) showed a statistically significant benefit over MMF monotherapy and a marginal, non-significant benefit over CSA monotherapy.
Conclusions:
- Oral MMF demonstrates immunosuppressive effects in corneal transplantation.
- Combination therapy with CSA and MMF provides a marginal survival advantage without increased toxicity.
- These findings support the potential of MMF and CSA in managing corneal graft rejection.
