Status and prospects for the development of regenerative therapies for corneal and ocular diseases.

Among the regenerative therapies being put into clinical use, the field of corneal regenerative therapy is one of the most advanced, with several regulatory approved products. This article describes the progress from initial development through to clinical application in the eye field, with a particular focus on therapies for corneal epithelial and endothelial diseases that have already been regulatory approved as regenerative therapy products. The applications of regenerative therapy to the corneal epithelium were attempted and confirmed earlier than other parts of the cornea, following advancements in basic research on corneal epithelial stem cells. Based on these advances, four regenerative therapy products for corneal epithelial disease, each employing distinct cell sources and culture techniques, have been commercialized since the regulatory approval of Holoclar® in Italy as a regenerative therapy product for corneal epithelial disease in 2015. Corneal endothelial regenerative therapy was started by the development of an method to expand corneal endothelial cells which do not proliferate in adults. The product was approved in Japan as Vyznova® in 2023. The development of regenerative therapies for retinal and ocular surface diseases is actively being pursued, and these therapies use somatic stem cells and pluripotent stem cells (PSCs), especially induced pluripotent stem cells (iPSCs). Accordingly, the eye field is anticipated to play a pioneering role in regenerative therapy development going forward.