Intraretinal transplantation to prevent photoreceptor degeneration

There is great interest in the potential of transplantation to treat retinal degenerative diseases in humans; however, there are still fundamental questions to be addressed in experimental animal studies. We have concentrated on two of these using the Royal College of Surgeons (RCS) rat as a suitable animal model. Firstly, does the loss of photoreceptors lead to secondary changes in the inner retina, which might compromise any photoreceptor preservation strategy? Analysis has shown that there are not only histochemical changes in the inner plexiform layer but also degeneration of retinal ganglion cells. The latter, occurring as a result of a vascular event, appears to have a parallel in some human retinal degenerative diseases. Secondly, what are the functional implications of the progressive photoreceptor loss in the RCS rat and how may transplantation prevent or slow that process? A progressively enlarging visual field defect can be demonstrated in these rats which can be stabilized by transplantation of retinal pigment epithelial cells. There is also a loss or diminished performance in a variety of visual tasks, although the rate of deterioration depends on the task; this too can be limited by cell transplantation. Current results indicate an optimistic future for transplantation in human retinal degenerative disease, but also emphasize the many preparatory steps that still have to be made for a successful clinical outcome.