Effect Of Alpha-gal On The Corneal Xenotransplantation In Gal Knockout Mouse Model

Abstract

Purpose: : To investigate the effect of Galα1-3Galβ1-4GlcNAc-R (α-Gal) on porcine xenocorneal graft survival and production of anti-Gal antibodies in Gal knockout mouse model.

Methods: : C57BL/6 (B6) and α1,3-galactosyltransferase knockout (GTKO) mice were divided into 5 groups and underwent orthotopically full thickness corneal transplantation as follows (n=4 for each group); (1) group 1: B6 to B6, (2) group 2: fresh porcine posterior corneal lamella to B6, (3) group 3: fresh porcine posterior corneal lamella to GTKO, (4) group 4: decellularized porcine posterior corneal lamella to GTKO, and (5) group 5: B6 to GTKO. Before transplantation, all GTKO recipients were sensitized using intraperitoneal injections of rabbit red blood cells. Median survival time (MST) was compared between groups and serum concentrations of IgG/IgM anti-α-Gal antibodies were evaluated at 1 week, 2 weeks, and 4 weeks.

Results: : There was no hyperacute rejection showing MST was around 11 days in all of the groups (p=0.528, Log-Rank test). There were no changes in IgM anti-α-Gal antibodies in all groups, which corresponded well with clinical survival data. While, IgG anti-α-Gal antibody was gradually elevated over time in fresh porcine grafted GTKO recipients.

Conclusions: : Our findings suggest that α-Gal is less likely to induce hyperacute rejection but may affect the long term survival via antibody mediated rejection in corneal xenotransplantation.

Keywords: transplantation • cornea: basic science • cornea: clinical science