Effect of Cyclosporin A, Rapamycin, and FK-506 on corneal epithelial cells and lymphocyte proliferation

The proliferation of corneal epithelial cells in vitro is relatively resistant to the addition of immunomodulating drugs to the cultures. Cyclosporin A, FK-506, and Rapamycin cause minimal or no inhibition of corneal epithelial cells proliferation in concentrations of up to 500 ng/ml. At concentrations of 5000 ng/ml, all drugs induce an inhibitory effect. In this system, Rapamycin induces the strongest inhibition in most cases. Nonetheless, a residual activity of more than 50% is recorded even at the highest concentrations. On the lymphocytes, both FK-506 and Rapamycin show marked inhibitory effects at 0.5 ng/ml, while CsA shows significant inhibition only at the level of 50 ng/ml or higher. These data can be interpreted to indicate a possible large therapeutic window (marked inhibition of lymphocyte proliferation at drug concentrations which do not have any effect on epithelial cell proliferation) of these drugs for topical use in external ocular diseases.