MISOPROSTOL WITH CYCLOSPORINE-A PROLONGS CORNEAL ALLOGRAFT SURVIVAL IN AN ANIMAL-MODEL

Cyclosporin A (CSA) has been shown to prolong corneal allograft surviv al in a variety of animal models. Misoprostol is a prostaglandin E(1) analogue with oral bioavailability and immunosuppressive properties, M isoprostol and CSA are synergistic immunosuppressants in vitro. In the present study, we evaluated the effect of adding misoprostol to a sub therapeutic dose of CSA in the orthotopic allogeneic rat penetrating k eratoplasty model. Seventy inbred Lewis rats were recipients of orthot opic corneal allografts from Brown-Norway donors. Ten Lewis rats recei ved orthotopic syngeneic grafts (Lew to Lew). Two separate experiments with 40 animals per trial were performed. In each trial, the rats wer e divided equally into four groups. Trial A: allogeneic control (A1), syngeneic control (A2), CSA at 10 mg/kg/d (A3), and CSA at 15 mg/kg/d (A4). Trial B: allogeneic control(B1), CSA alone at 7.5 mg/kg/d (B2), misoprostol alone at 1 mg/kg/d (B3), and CSA with misoprostol at 7.5 a nd 1 mg/kg/d, respectively (B4). Syngeneic control A2 as well as group A4 remained clear through postoperative day 22, The allogeneic contro l groups A1 and B1, plus treatment groups B2 and B3, rejected their gr afts by postoperative day 12. Groups A3 and B4 demonstrated a delay in allograft rejection that continued to be statistically significant th rough the 12th postoperative day (p < 0.001). We conclude that the add ition of systemic misoprostol to CSA can effectively prolong corneal a llograft survival in the orthotopic allogeneic rat penetrating keratop lasty model.