CHARACTERISTICS OF CORNEAL XENOGRAFT REJECTION IN A DISCORDANT SPECIES COMBINATION

Purpose. To characterize the fate of Lewis rat corneas transplanted to Hartley guinea pigs. Methods. Full-thickness Lewis rat corneal button s were grafted orthotopically to Hartley guinea pigs (xenografts), ACI rats (allografts), or Lewis rats (isografts). Two panels of recipient s were presensitized with xenogeneic skin grafts or allogeneic skin gr afts. Serum samples were collected pre- and post-transplant and analyz ed by flow cytometry and indirect immunofluorescence. Results. Unlike vascularized xenografts that reject within 30 min, corneal xenografts had a mean survival time of 8 days. Presensitization with guinea pig s kin grafts increased recipient IgM and IgG xenoantibody levels, as mea sured by flow cytometry on guinea pig hematopoietic cells, and signifi cantly accelerated corneal xenograft rejection with a mean survival ti me of 5 days. Presensitization with allogeneic ACI skin grafts had no effect on xenoantibody levels or xenogeneic corneal graft survival. Gu inea pig corneas stained by indirect immunofluorescence with normal ra t serum exhibited low (1+) but significant binding of IgG and IgM, pri marily on epithelium and stroma. Serum from Lewis rats that rejected a corneal xenograft had elevated IgG and IgM xenoantibodies that reacte d strongly (4+) with guinea pig cornea and heart. Conclusions. In the discordant guinea pig-to-rat species combination, donor corneas expres s xenoantigens; rejection of corneal xenografts stimulates IgM and IgG xenoantibody production; sensitization to xenoantigens can accelerate corneal xenograft rejection; and discordant corneal xenografts, unlik e vascularized organs, are not hyperacutely rejected.