Long-term photoreceptor transplants in dystrophic and normal mouse retina

Purpose. To determine the long-term status of transgenic photoreceptors transplanted to the subretinal space of both rd mutant (receptorless) and normal mouse retina. Methods. Microaggregates of neural retina from transgenic mice containing lacZ-labeled photoreceptors were transplanted to the subretinal space of adult rd mutant and normal mice. The transplant site was examined by light and electron microscopy at monthly intervals up to 9 months after transplantation surgery. Results. Photoreceptors develop and survive well if transplanted with the proper orientation to the retinal pigment epithelium (RPE). The status of the photoreceptors, including outer segments and synaptic terminals, appear normal for at least 9 months after transplantation; they continue to express the lacZ reporter gene. Cones survive as well as rods. Transplants to the normal mouse develop normally, whereas the host photoreceptors displaced from the RPE degenerate. A barrier formed by Muller cell processes, develops after photoreceptor degeneration in both normal and rd mouse retina and demarcates host from transplant tissue. Areas can be found in which neural processes have penetrated this barrier. There is no evidence of host-graft rejection. Conclusion. Transplanted progenitor photoreceptors develop and survive well for long periods of time in either the rd mutant or normal retina if they are properly positioned. In the former, they reconstitute a photoreceptor layer; in the latter, they replace the host photoreceptor layer, which degenerates after being displaced from the RPE. Areas of potential contact between donor and host neurons exist in these transplants.