Photoreceptor Transplantation and Regeneration

A recent study showed that an electronic chip implanted under the human retina restored some extent of vision to a blind patient. Because the device was implanted where the light sensitive cells, the photoreceptors, should have been, this study demonstrated that it is possible to take advantage of the internal circuitry of the retina even in the absence of photoreceptors and in the presence of extensive glial and neuronal reorganization. This result strongly supports the development of cell replacement therapies for the cure of photoreceptor degeneration, provided that the cells are implanted in the same anatomical location. Similarly to other sensory neurons but differently from neurons lost in most degenerative diseases, photoreceptors are the first neurons of the circuit and only have to make efferent connections. Secondly, photoreceptors are histologically located in a restricted region of the organ. These features make them the most immediately transplantable type of neuron and interesting candidates for clinical trials involving cell transplantation. In cell replacement therapies the identification of the source of cells able to integrate and connect to the host tissue needs to be defined. For the retina, cells showing the best survival and integration rates are post-mitotic rod precursors, rather than immature retinal progenitors. Given the difficulty of obtaining human fetal cells, many studies are undergoing to differentiate cells with such features starting from stem cells. Three main classes of stem cells are under investigation to be sources for in vitro photoreceptor generation. They are embryonic stem cells, induced pluripotent stem cells and adult retinal stem cells. This chapter will describe the current preclincal studies for in vitro generation and subsequent transplantation of photoreceptor precursors.