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Transplanted pluripotent stem cell‐derived photoreceptor precursors elicit conventional and unusual light responses in mice with advanced retinal degeneration

Retinal dystrophies often lead to blindness. Developing therapeutic interventions to restore vision is therefore of paramount importance. Here we demonstrate the ability of pluripotent stem cell‐derived cone precursors to engraft and restore light responses in the Pde6brd1 mouse, an end‐stage photoreceptor degeneration model. Our data show that up to 1.5% of precursors integrate into the host retina, differentiate into cones, and engraft in close apposition to the host bipolar cells. Half of the transplanted mice exhibited visual behavior and of these 33% showed binocular light sensitivity. The majority of retinal ganglion cells exhibited contrast‐sensitive ON, OFF or ON‐OFF light responses and even motion sensitivity; however, quite a few exhibited unusual responses (eg, light‐induced suppression), presumably reflecting remodeling of the neural retina. Our data indicate that despite relatively low engraftment yield, pluripotent stem cell‐derived cone precursors can elicit light responsiveness even at advanced degeneration stages. Further work is needed to improve engraftment yield and counteract retinal remodeling to achieve useful clinical applications.