Retinal epithelial cell transplantation has provided a means to stop a hereditary retinal degeneration from progressing in one of the most well known animal models of such diseases, the RCS (Royal College of Surgeons) strain of rats, raising the hopes that other forms of retinal degenerations may also be treated in this way. This discovery was made independently by Turner and Li at Bowman Gray School of Medicine and our own group at Columbia University's College of Physicians and Surgeons. This achievement rests on much previous research on the RCS rat. This hereditary retinal degeneration was discovered in 1938'but it was not until 19622 that Dowling and Sidman detected by electron microscopy a significant clue to its pathophysiology, the pile-up of outer segments. We now know that a defect in the retinal epithelial cells of the dystrophic animals prevents them from phagocytizing the growing tips of the outer segments and this leads to destruction of the photoreceptor cells across the entire retina. 3" 8 This is one of the only models of a hereditary retinal degeneration where the defect is linked to a specific type of retinal cell, although the molecular defect is still being sought. The breeding of a congenic strain of these rats by La Vail and associates in" which both normal and affected animals share virtually the same genome, except for the defective retinal gene and another gene for pigmentation, 9 makes this animal model an optimal system to examine the efficacy of retinal epithelial cell transplantation for modifying the disease, because host graft rejection should be minimal. Retinal epithelial cell transplantation was first reported in 198310 and by 1988 was being done in at least three different laboratories, Columbia University in New York, 13" 18 Bowman-Grey School of Medicine in Winston-Salem18" 20 and the Institute of Ophthalmology in London. 21-22 The former two laboratories had turned their attention to the RCS rat, one using an anterior transvitreal approach, 16 the other a posterior transchoroidal approach. 20 Both used jet stream force to dislodge host retinal epithelium before injecting freshly dissociated cells from the normal rat into the subretinal space of the dystrophic rat. The results were striking. Photoreceptors were preserved in the vicinity of the transplant cells at 4 to 5 months of age. In the untreated RCS rat virtually all of the photoreceptors had degenerated at 2 months of age.

At present, the results raise some interesting questions. It is tentatively considered that survival depends upon reestablishing phagocytosis of outer segment material by the normal retinal epithelium. Some photoreceptors survive, however, near but not directly contiguous with transplant cells. Is this due to the fact that the transplanted cells migrate around in the subretinal space? Or is there some humoral factor that diffuses from normal to transplant cells? Or do shed outer segments find their way to more distant retinal epithelium? Further work with this method may reveal the answers to these questions. It also reveals that transplantation can shed new light on the pathophysiology of retinal disease. Such an approach could, for example, reveal whether other animal models for retinal degeneration are due to defects in the retinal epithelium and/or the photoreceptors. It is difficult to predict the future of retinal epithelial cell transplantation. In our opinion the major challenge that must be met, in order to bring this method to bear on human retinal disease, lies in the microsurgical technology needed to operate in the subretinal space. The current technique for epithelial cell transplantation is still somewhat crude because host cells must be dislodged by jet stream …