Cyclosporine treatment promotes survival of human fetal neural retina transplanted to the subretinal space of the light-damaged Fischer 344 rat

Abstract

We have reported that xenografts of human fetal neural retina survive in the subretinal space of cyclosporine-immunosuppressed rats. In view of the current controversy regarding the role of cyclosporine, we wished to determine if cyclosporine immunosuppression was an absolute requirement for retinal xenograft survival. Neural retinas from human fetal eyes obtained within 1 h of termination of pregnancy were stored in Optisol medium (Chiron Vision, Irvine, CA) at 4°C for 2 and 7 days. Retinas were then transplanted to the subretinal space of either cyclosporine-treated (10 mg/kg/day) light- damaged Fischer 344 rat eyes (17 animals, 28 eyes) or to the subretinal space of light-damaged Fischer 344 rat eyes (9 animals, 15 eyes) receiving no cyclosporine treatment. Grafted eyes were observed clinically at 10, 20, and 30 days posttransplantation. At 30 days, the animals were sacrificed and the grafts observed histologically. Human fetal retina xenografted to the subretinal space of immunosuppressed rats survived (9/17 animals, 12/28 eyes), showed good integration with the host retina and initial photoreceptor differentiation. Tissue xenografted to the subretinal space of non-cyclosporine-treated rats was not observed to survive (0/9 animals, 0/15 eyes). A low level cellular reaction was seen around three of the injection sites within the nonimmunosuppressed rats. We conclude that immunosuppression is necessary for the survival of human fetal neural retina xenografted to the subretinal space.