Characterization of Porcine Corneal Endothelium for Xenotransplantation

Abstract

Purpose: Endothelial keratoplasty (EKP) has become increasingly popular in the treatment of corneal disease. However, the global shortage of human donor corneas limits clinical corneal transplantation. Genetically engineered (GE) pigs may provide an alternative source of corneas for EKP. The aim of this study was to evaluate corneal endothelial cells (CECs) from wild-type (WT) and GE pigs. Methods: Density, size of CECs, and the percentage of hexagonal cells (as a measure of heterogeneity) were measured by ex vivo confocal microscopy in corneas from WT and GE pigs of different ages – neonatal (4–5 days), young (5–15 weeks), adult (5–15 months), and old (20–42 months). α1,3-galactosyltransferase gene-knockout (GTKO) pigs transgenic for the human complement-regulatory protein(s), CD46 (GTKO/CD46) +/− CD55 (GTKO/CD46/CD55) were used as sources of GE corneas. Results: Mean CEC densities (cells/mm2) were neonatal (5968), young (3789), adult (2589), and old (2070). As with human corneas, there was an age-dependent decrease in pig CEC density and increase in pig CEC size. However, unlike human corneas, there was no correlation between the percentage of hexagonal cells (approximately 50% in all pig corneas) and age, suggesting that heterogeneity is intrinsic for pig corneas. Genetic modification did not affect CEC density, size, or morphology compared to WT pigs. Conclusion: Because of the availability of young pigs and their greater CEC density (and the protection afforded against the human immune response), GE pigs could provide an unlimited source of corneas for clinical EKP.