FK-506 DELAYS CORNEAL GRAFT-REJECTION IN A MODEL OF CORNEAL XENOTRANSPLANTATION

FK-506 is a relatively new immunosuppressant similar in action to cycl osporine A, but is much more potent. Its primary action is against T l ymphocytes, the major cellular component in corneal allograft rejectio n. The purpose of this study was the evaluation of the ability of topi cal and systemic FK-506 in preventing corneal xenograft rejection in a n experimental animal model. Cross-species xenotransplants were used a s the most vigorous stimulus to induce corneal rejection. Corneas deri ved from Hartley guinea pigs were transplanted into the left eyes of 3 2 male Lewis rats. Topical treatment was administered by using FK-506 0.3 mg/ml in a cyclodextrin suspension or vehicle (cyclodextrin suspen sion) four times per day. For systemic treatment, 0.5 mg/kg/day of FK- 506 or vehicle (saline) was administered intraperitoneally. Treatments were started 60 minutes after surgery and continued for 21 days. The grafts underwent a double-masked examination, and a score was given fo r clarity, edema, and vascularization. The animals were sacrificed 21 days after transplantation. The control groups had allograft rejection after 6.75 +/- 0.31 (topical vehicle) and after 7.37 +/- 0.32 (system ic vehicle) days. The FK-506-treated groups showed allograft rejection after 14 +/- 0.88 (topical FK-506) or after 16.25 +/- 1.23 (systemic FK-506) days. In addition, FK-506-treated rats manifested less corneal neovascularization than control animals. We conclude that systemic or topical FK-506 is effective in prolonging xenograft survival in the r at keratoplasty model.