Optimisation of human ESC-derived photoreceptor cell differentiation

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Retinal degenerations, in which the light-sensing photoreceptor cells of the eye are lost, are a major cause of untreatable blindness in the UK. Inherited sight loss affects 1 in 3,000 of the population, and age-related macular degeneration (AMD) affects 1 in 10 people over 60 yrs. Currently there are no treatments that can restore sight and thus there is a need to develop new therapeutic approaches. As the majority of the neural connections remain following retinal disease, new photoreceptors need only make short, single connections to the remaining retinal cells to contribute to vision. Therefore, retinal repair by the transplantation of new photoreceptors to the diseased retina represents one of the most feasible types of CNS repair.We have previously made important breakthroughs regarding cell transplantation therapy for retinal repair. In landmark studies, we have demonstrated that photoreceptor cells can be transplanted into an adult retina and restore vision in animal models of retinal degeneration, provided the photoreceptor cells are at the correct stage of development. It is not practical to develop treatments based on obtaining photoreceptor cells from human fetuses and we therefore need to generate photoreceptor cells in the laboratory from human embryonic stem cells. Following the discovery by other groups that embryonic stem cells can spontaneously self-organise and develop into a retina if placed in the right conditions in a three-dimensional culture system, we have shown that we can produce photoreceptors that are suitable for transplantation from mouse embryonic stem cells grown in a dish. In this project we propose to develop a methods to generate, purify and store human photoreceptor precursors that are suitable for transplantation from clinical-grade human embryonic stem cells in order to determine the best cell lines and protocols for clinical application. This project will provide essential underpinning for the development of future clinical trials and the translation of our stem cell therapy programme into the clinic.