Photoreceptor replacement therapy using a tissue scaffold shows evidence of donor-host integration in non-human...

Retinal degeneration is characterized by progressive photoreceptor (PR) loss, leading to visual impairment and ultimately blindness. PR replacement is a promising therapeutic strategy, but surgical delivery remains challenging, and efficacy in primates remains unknown. Tissue scaffolds hold potential for better control over cell delivery and distribution. Here, we delivered a scaffold, loaded with human embryonic stem-cell-derived PR precursors (PRPs), to the subretinal space of a non-human primate (NHP) and monitored donor PR survival and morphology in vivo. A substantial fraction of donor PRs survived for 20-weeks, with neurite extension by week 7 and some morphological elongation by week 17. Immunolabeling confirmed donor PR survival at 20 weeks with expression of key phototransduction and ribbon proteins, and some donor PRs forming putative synapses with host bipolar cells (BCs), including midget BCs. These findings suggest that scaffold-mediated PR replacement holds promise for restoring high acuity foveal vision.