Corneal allograft rejection has become a leading cause of graft failure. Previous studies by the Principal Investigator have demonstrated that experimental corneal allografts that have been soaked in either heterologous or homologous antibody against histocompatibility antigens have prolonged survival times and decreased incidence of rejection as compared to unsoaked grafts or those soaked in normal serum solutions. Experiments to date appear to rule out blockage of efferent rejection mechanisms as a basis of the protection. The proposed studies will elucidate the biological characteristics of histocompatibility antigens on corneal cells (with special emphasis on Ir antigens), the physiologic and immunologic alterations of corneas and corneal cells by changing physical parameters or exposure to antibody against histocompatibility antigens, the fate and systemic localization of corneal cell histocompatibility antigen-antibody complexes, and the immunologic basis for the protection of corneal allografts by soaking in antibody or changing physical parameters. Improved methods for prolonging survival of corneal allografts that are easily applicable to humans will be sought. Extensive use will be made of in vitro studies using cultured cornneas or corneal cells plus lymphocytes. Fluorescent antibody and immunoperoxidase methods will be used to identify histocompatibility antigens and antibody against them in vitro and in vivo. In addition, radioisotope labelling will be used in conjunction with liquid scintillation counting and radioautography for more precise quantitation and localization. Extensive use of inbred animals will allow investigation as well as to allow the application of methods to eliminate Ir antigens from donor corneas.
