Retinal degenerative diseases often involve the loss of cone photoreceptors in the macula, located near the centre of the retina. Current methods to replace the macula, such as generating grafts from retinal organoids, are limited and not scalable for clinical application. Here, Gilbert Bernier and colleagues demonstrate that retinal sheets generated from human induced pluripotent stem cells (iPSCs) can be transplanted into a minipig model of retinal degeneration and integrate with the host tissue. The authors first use single-cell RNA sequencing to confirm that the retinal sheets contain all cell types in the human eye. For retinal transplantation, the authors isolate retinal sheet ‘punches’ that are enriched with late retinal progenitor and photoreceptor precursor cells. These punches can be cultured long-term and differentiate into mature cone photoreceptors. When the punches are transplanted into a minipig model of severe photoreceptor degeneration, the grafts can integrate into the host's damaged retina and recreate a new, immature, photoreceptor layer. Functional assays suggest the grafts can respond to light stimuli, and there is evidence of synapse formation between the grafted photoreceptors and the host neurons. Overall, the findings provide a comprehensive characterisation of retinal sheets produced from iPSCs and demonstrate the potential of retinal sheet transplantation for clinical applications.
