Retinal Transplants: Growth Differentiation Integration Organization and Survival

Abstract: The goal of the study was to get a better understanding of factors controlling the growth, differen-tia-tion, integration, organization and survival of retinal transplants, with the long-term view of eventually developing retinal transplantation into a clinically useful procedure for treating degenerative retinal disorders such as retinitis pigmentosa. Embryonic day 15 rabbit retinas were transplanted into adult rabbit eyes and were allowed to survive for various times. Aspects of growth, differentiation, integration and long-term survival were studied. A new transplantation tech-nique was also developed permitting transplantation of large pieces of retina with minimal surgical trauma. Analyses of the appearance of protein Ki-67 (found only in dividing cell nuclei) in developing normal and transplanted retinas showed that transplants maintain their normal pattern of proliferation. Glial cells at the host-graft interface proliferate excessively. Analyses of nitric oxide synthase in developing normal and transplanted retinas demonstrated that transplanted cells maintain their normal differentiation chronology. Further, nitric oxide synthase immunoreactive cells were found to extend long processes into the inner plexiform layer of the host retina, demonstrating that transplanted neurons are capable of projecting to appropriate places in the host retina. Large-sheet transplants developed better in the subretinal space than in the epiretinal and surgical injury evidently plays a major role in rosette formation. After long survival times (2 years) massive gliosis appears in some retinal transplants, but neurons survive in others. Photoreceptors survive only if they are well apposed to the host pigment epithelium. The outer nuclear layer of the host retina degenerates in parts covering the transplant, but its inner retinal layers remain functional and in principle capable of receiving graft connections for long times.