Inherited and aging retinal diseases are the leading causes of blindness. Significant advancement has been made in developing gene and cell therapeutic interventions for these retinal diseases. Vision depends on the functional interplay between the different retinal cell layers: the retinal pigmented epithelial (RPE), photoreceptor layer, and ganglion cell layer. The photoreceptor layer is photosensitive and is mainly populated with rods and cones. The monolayer RPE is located underneath the photoreceptor outer segments, supporting the key visual cycle activity and phagocytosis of the outer segments. The ganglion cells receive information from photoreceptors via interneurons, thereby propagating the visual stimulus information to the brain. Loss of critical retinal gene function or the retinal cell layer is irreversible and could lead to vision loss. Therefore, the development of reproducible methods and tools for functional gene and cell replacement in the retina is paramount to treating stage-specific retinal diseases.

This Methods Collection introduces novel protocols for generating retinal cells from human pluripotent stem cells, as well as transplantation techniques in various pre-clinical animal models. The focus is on the following:

1. Reproducible methods to generate RPE, photoreceptors, and ganglion cells from human pluripotent stem cells.
2. Transplantation methods to deliver the genes and cells into the diseased retinas of different animal models.
3. Functional assays to assess visual function in the gene-treated or cell-transplanted animals.