WZS-pig is a potential donor alternative in corneal xenotransplantation

Purpose: To explore the characteristics of rejection of Wuzhishan (WZS) pig-to-rhesus monkey corneal transplants and to evaluate WZS pig corneas as potential donor material for a clinical setting. Methods: Wuzhishan pigs were used as donors and rhesus monkeys as recipients for corneal xenotransplantation. Eighteen rhesus monkeys were divided into three groups. Groups 1 and 2 underwent penetrating corneal xenotransplantation, while group 3 underwent lamellar corneal xenotransplantation. Only group 2 received subconjunctival injections with betamethasone for 3 months. All xenografts were evaluated by slit-lamp microscopy. Two recipients in each group were killed for corneal histopathological staining at 30 days after surgery. The concentrations of cytokines in the aqueous humor were detected by cytometric bead array. Results: Rejection of the xenografts occurred at approximately 15 days after surgery in group 1. Rejection was delayed for more than 4 months by conjunctival injection with betamethasone (group 2). Use of lamellar corneal xenografts (group 3) maintained corneal transparency for more than 3 months. Histopathological examination in group 1 showed that the xenografts were infiltrated with inflammatory cells. The corneal endothelia were destroyed and exudative membranes were formed in the anterior chamber. However, in the betamethasone-treated group, the corneal xenografts showed only minimal edema and almost no inflammatory cell infiltrate. The corneal endothelia were intact and there was no exudative membrane formation. The concentration of interleukin (IL)4, IL5 and IL10 showed an increased shift 3 weeks after surgery in group 1 and 2, but no change of cytokine's concentration was found in group 3. Conclusions: Rejection of pig-rhesus xenografts occurred early in penetrating corneal transplantation, but not in lamellar corneal transplantation. The endothelium of the xenograft might be a primary target of immune attack. Corticosteroid treatment inhibited rejection of the corneal xenografts.