USE OF TOPICAL FK506 IN A CORNEAL GRAFT-REJECTION MODEL IN LEWIS RATS

Purpose. To evaluate the immunosuppressive effect of topical FK506 on allograft corneal rejection in rats. Methods. Lewis rats were used as recipients and Fisher rats as corneal graft donors. In Experiment 1, a ll rats received intraperitoneally FK506 (0.3 mg/kg per day) for 7 day s to ensure equal baseline parameters. The rats then were assigned ran domly to treatment with topical 0.3% FK506 or vehicle alone. In anothe r set of experiments, rats were treated only with topical treatment. T he grafts were inspected by clinical evaluation. Corneas obtained at t he time of maximum rejection were used for histology and immunohistoch emistry. Results. The selected combination of rat strains caused 100% graft rejection in untreated animals within 2 weeks after the penetrat ing keratoplasty. In the treated animals, rejection was delayed until the end of topical therapy. One third of corneal grafts remained clear until day 30. Histologic and immunohistochemical studies confirmed th e clinical evaluations. Untreated rat corneas had a large number of in filtrating helper-inducer T cells, macrophages, interleukin-2 receptor -expressing cells, and Ia-antigen-expressing cells. At the same timepo int, topically treated corneas showed a limited inflammatory response characterized by a 2/3 reduction in the number of infiltrating helper and cytotoxic cells, and a five-fold decrease in the expression of cla ss I and class II major histocompatibility antigens. Conclusions. Topi cal FK506 treatment is an effective way of preventing corneal graft re jection in the Lewis rat corneal graft model. It shows promise as a dr ug to prevent corneal graft rejection in humans.