"Retinal degenerations leading to loss of photoreceptors are a major cause of untreatable blindness in the EU. Age-related macular degeneration (AMD) affects 1 in 10 people over 60 yrs. Currently no treatments restore lost photoreceptor cells and visual function and thus there is a need for new therapeutic approaches. We have shown previously that transplantation of rod precursor cells at a specific stage of development results in integration and differentiation into rod photoreceptors (Nature, 2006) and that this can improve vision in mouse models of visual dysfunction (Nature, 2012). These studies provide proof-of-concept for effective transplantation of neurons and the basis for ES cell-derived photoreceptor transplantation. Importantly, these results are only achieved using photoreceptor precursor cells that are specified to differentiate into photoreceptors, but are not mature photoreceptors at the time of transplantation. The objective of this proposal is to determine if ES/iPS cell-derived photoreceptors can be utilised as a therapeutic source of cells to repair the degenerate retina and to model photoreceptor disorders. We will build on our achievements in the field of donor photoreceptor cell transplantation and determine if mouse and human ES cells have the potential to provide an efficient source of rod photoreceptor precursors for restoring vision. A key requirement for the development of retinal stem cell therapy is effective generation and transplantation of ES-derived cone photoreceptor precursors. We will modulate differentiation pathways in order to enrich for cone precursors and investigate their ability to restore visual responses in animal models of cone dysfunction. Finally, we will develop protocols for generating mature photoreceptor cells with outer segments from human iPS cells in order to model photoreceptor disease."