Corneal Transplant Survival in Young Mice

Abstract

Purpose : Corneal transplantation in children yields significantly lower survival rates (< 30%) than in adults (>90% survival). Thus, it is of interest to gain a better understanding of the immunological mechanisms contributing to graft rejection in very young recipients. In this study we established a mouse model of corneal transplantation in very young graft recipients. We determined the kinetics of allograft rejection and the contribution of innate immune cells in young vs. adult allograft rejection.

Methods : Allogeneic orthotopic corneal transplantation was carried out on 3.5-week-old and 10-week-old BALB/c recipients using C57BL/6 mice as donors (n=10/group). Grafts were examined weekly until eight weeks to evaluate graft survival. Standardized opacity and neovascularization grading systems were used. Opacity scores above 2 (i.e. a level of opacity that obscures recognition of iris details) were considered as rejected. Frequencies of Natural Killer (NK) cell infiltration into the grafts were assessed using flow cytometry.

Results : Corneal allograft survival was significantly lower in 3.5 compared to 10-week-old mice at 8 weeks post-transplantation (0% vs. 50%, with median survival of 35 vs. 49 days, P=0.0051). Corneal opacity scores were significantly higher in 3.5 vs. 10-week-old recipients from 3 to 8 weeks post-transplantation (P<0.05). In addition, corneal neovascularization was significantly higher in 3.5 compared to 10-week-old mice at 2 and 3 weeks post-transplantation (P<0.01). The frequencies of CD49b+ NK cells in the cornea were significantly higher in 3.5 compared to 10-week-old mice at 14 days after transplantation (3.95% vs. 0.10%; P<0.001).

Conclusions : These data suggest an increased and accelerated corneal allograft rejection in very young compared to adult mice. Increased graft opacification and neovascularization may be due to enhanced NK cell infiltration in the cornea. Strategies to modulate innate immune responses may enhance corneal allograft survival in the very young.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.