Objective: To investigate the effects of rapamycin on prevention of corneal allograft rejection in murine corneal transplantation.
Methods: The outbred strain SD and Wistar rats were used as donors and recipients, respectively. Sixty-eight Wistar rats were divided into four groups: Group A, autograft control; Group B, allograft control (the control groups were given placebo only); Group C and D, allograft groups, were treated with orally RAPA (3 mg.kg(-1).d(-1)) and CsA (10 mg.kg(-1).d(-1)), respectively. The drugs were delivered for 12 days beginning at the day of transplantation. Each animal was examined by operating microscopy. The grafts were evaluated clinically by means of Holland's scoring system and graft survival was assessed by Kaplan-Meier analysis. The neovascular indexes of rejection were compared among different groups. Histological examination on ocular tissues was performed on day 14 to confirm the clinical diagnosis of rejection.
Results: The average transplant survival time in the allogenic control (Group B) was (11.0 +/- 1.5) d. Treatment with RAPA (Group C) led to a statistically significant prolongation of transplant survival to (36.1 +/- 14.9) d (P < 0.05). Treatment with RAPA 3 mg.kg(-1).d(-1) prolonged transplant survival as compared with treatment with CsA (Group D), but the difference was not statistically significant (P > 0.05). Corneal neovascularization was induced after the surgery. In RAPA group, corneal neovascularization was markedly reduced as compared with allograft control (Group B) (P < 0.05) and CsA group (Group D) (P < 0.05). Fewer inflammatory cells were found in the corneal stroma of the RAPA group.
Conclusion: These results show that oral immunosuppression with RAPA can prevent corneal graft rejection and corneal neovascularization.