Challenges and Advances in the Production of Transplantable Retinal Tissue from Retinal Organoids.

Retinal degenerative diseases (RDD), which impair photoreceptors, the retinal pigment epithelium (RPE), and associated retinal cells, result in severe vision loss. For patients with advanced RDD, tissue replacement therapies, such as transplantation, offer potential pathways to visual rehabilitation. While fetal retinal transplantation has shown some promise in preclinical and clinical studies, human pluripotent stem cell (hPSC)-derived retinal organoids (ROs) present a promising alternative. ROs are three-dimensional tissues that replicate key aspects of retinal development, making them viable candidates for transplantation. However, the path toward clinical application faces two primary challenges: achieving Good Manufacturing Practice (GMP)-compliant production and overcoming technical difficulties associated with safe transplantation. Current RO production protocols are often limited by variability in tissue morphology, yield, and reproducibility, while transplantation efforts are hindered by rosette formation and mechanical damage to the subretinal space. Recent innovations, including automated bioreactor systems and optimized surgical techniques, offer potential solutions. Further advances in understanding and preventing rosette formation are essential to improve transplantation outcomes. Continued research and technological development are necessary to unlock the full potential of ROs for visual rehabilitation in patients with retinal degeneration.