Transplantation of genome-edited retinal organoids restores some fundamental physiological functions coordinated with severely degenerated host retinas.

Abstract

We have previously shown that the transplantation of stem cell-derived retinal organoid (RO) sheets into animal models of end-stage retinal degeneration can lead to host-graft synaptic connectivity and restoration of vision, which was further improved using genome-edited Islet1^-/- ROs (gROs) with a reduced number of ON-bipolar cells. However, the details of visual function restoration using this regenerative therapeutic approach have not yet been characterized. Here, we evaluated the electrophysiological properties of end-stage rd1 retinas after transplantation (TP-rd1) and compared them with those of wild-type (WT) retinas using multi-electrode arrays. Notably, retinal ganglion cells (RGCs) in TP-rd1 retinas acquired light sensitivity comparable to that of WT retinas. Furthermore, RGCs in TP-rd1 retinas showed light adaptation to a photopic background and responded to flickering stimuli. These results demonstrate that transplantation of gRO sheets may restore some fundamental physiological functions, possibly coordinating with the remaining functions in retinas with end-stage degeneration.