Retinal organoid differentiation strategies and their application in retinal degenerative disease modeling

Abstract

The retina is a specialized, light-sensitive tissue comprising multiple cell types that convert light into neural signals for vision. Retinal degenerative diseases remain a major cause of irreversible vision loss worldwide, underscoring the need for suitable in vitro models to elucidate disease mechanisms and investigate therapeutic strategies. Three-dimensional (3D) retinal organoids derived from human pluripotent stem cells (hPSCs), including human embryonic and induced pluripotent stem cells, have emerged as a powerful tool for modeling these conditions. Several protocols have been established, notably fully 3D floating cultures, a hybrid 3D/2D/3D approach initiated with embryoid bodies, and a combined 2D/3D system starting with confluent hPSC cultures. Despite their promise, challenges persist in scalability and reproducibility, fully recapitulating the complexity of the native retina. This chapter reviews the current state of retinal organoid research and highlights the application of gene editing and reprogramming to create patient-specific models of diseases such as age-related macular degeneration, glaucoma, and retinitis pigmentosa. By more accurately reflecting in vivo architecture compared to conventional cell lines and animal models, hPSC-derived retinal organoids offer valuable platforms for disease modeling, drug screening, and regenerative medicine, with ongoing innovations poised to address remaining hurdles.