Abstract

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. Up to 1.5% of precursors integrated into the host retina, differentiated into cones and formed synapses with bipolar cells. Half of the transplanted mice exhibited visual behaviour and 33% showed binocular light sensitivity. The majority of ganglion cells exhibited contrast-sensitive ON, OFF or ON-OFF light responses and even motion sensitivity. Many cells also exhibited unusual responses (e.g. light-induced suppression), presumably reflecting remodelling of the neural retina. Our data indicate that despite relatively low engraftment yield, engrafted 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 remodelling to achieve useful clinical applications.