PROLONGATION OF CORNEAL ALLOGRAFT SURVIVAL WITH LIPOSOME-ENCAPSULATEDCYCLOSPORINE IN THE RAT EYE

Purpose: To study the effects of different formulations of topical cyc losporine (Cyclosporin A [CsA]) on corneal allograft rejection in a ra t model. Methods: Female Lewis rats received penetrating keratoplastie s from female Wistar-Furth donors. A total of 78 allogeneic grafts wer e performed. An additional 15 syngeneic grafts (Lewis) were used as te chnical controls. Two CsA preparations with equivalent drug concentrat ions (2.1 mg/ml) were applied as drops: CsA encapsulated in large unil amellar liposomes (CsA-LIP) and CsA dissolved in olive oil (CsA-DR). A llogeneic grafts were randomly assigned to receive CsA-LIP or CsA-DR b eginning on the day of surgery five times daily for 10 days. Animals w ithout any treatment or receiving empty liposomes (EM-LIP) were used a s treatment controls. Grafts were graded three times weekly and a reje ction index was generated based on graft clarity, neovascularization, and vessel size. Results: All syngeneic grafts remained clear over the observation period of 60 days. Rejected allogeneic grafts without any treatment and those receiving EM-LIP or CsA-DR showed a mean survival time (+/- standard deviation) of 14 +/- 4, 14 +/- 5, and 14 +/- 4 day s, respectively. There was no significant difference in mean survival time between the grafts without any treatment and those in CsA-DR or E M-LIP treatment groups. The mean survival time of rejected grafts in a nimals receiving CsA-LIP was prolonged to 20 +/- 4 days. There was a s ignificant difference in the mean survival time between the CsA-LIP tr eatment group and groups receiving CsA-DR, EM-LIP, or no treatment (P less-than-or-equal-to 0.05). The Kaplan-Meier survival curve of the Cs A-LIP treatment group was significantly different from the other exper imental groups. The graft survival rate in the CsA-LIP group was 77%, whereas the rate was 37% in the non-treated group, 45% in the CsA-DR g roup, and 36% in the EM-LIP group. Conclusion: Encapsulation of CsA in liposomes might be a promising formulation for use in the prevention of corneal graft rejection.