PREVENTION OF CORNEAL ALLOGRAFT-REJECTION IN RATS TREATED WITH SUBCONJUNCTIVAL INJECTIONS OF LIPOSOMES CONTAINING DICHLOROMETHYLENE DIPHOSPHONATE

Purpose. The drug dichloromethylene diphosphonate (CL2MDP) encapsulate d in liposomes depletes macrophages but not other immunocompetent cell s. The authors investigated whether subconjunctival injection of CL2MD P containing liposomes (CL2MDP-LIP) could prolong survival of corneal allografts in rats. Methods. Male Fisher rats received orthotopic corn eal grafts of Dark Agouti origin. Rats were treated postoperatively wi th subconjunctival injections of 0.1 ml CL2MDP-LIP at the time of tran splantation and on days 2, 4, 6, and 8 after transplantation. Control groups received either liposomes containing phosphate-buffered saline subconjunctivally at the same time points or no additional treatment. Corneal grafts were evaluated every other day and were scored for neov ascularization, opacity, and edema. Immunohistologic evaluation was pe rformed 12 and 19 days after surgery. Results. Corneal grafts in both control groups were rejected within 17 days. In the C12MDP-LIP treated rats, grafts were not rejected during the maximum follow-up of 100 da ys. Cellular infiltration in these grafts was clearly reduced. There w as also a strong reduction in neovascularization of the cornea. Conclu sions, Rejection of orthotopic allogeneic corneal grafts could be prev ented by repeated subconjunctival injection of C121MDP-LIP.