Retinal Pigment Epithelium Regeneration by Induced Pluripotent Stem Cells; Therapeutic and Modelling Approaches on Retinal Degenerative Diseases

Retinal degenerative diseases (RDDs) are irreversible ocular damages categorized as retinopathies. RDDs affect about 0.05% of individuals worldwide. The degenerations of RPE cells are involved in inherited and age-related RDDs. After the invention of induced pluripotent stem cells (iPSC) by Yamanaka, a promising avenue has been opened to regenerative medicine and disease modeling. Retinal pigment epithelium (RPE) degeneration related-RDDs are also affected by iPSCs. IPSC-derived RPE cells created a novel method for treating the RPE degeneration related-RDDs and retinal diseases modeling to find a new therapeutic approach or drug development. There are various studies based on iPSC-derived RPE cells reporting the investigation of the role of a specific mutation, protein, signaling pathway, etc., responsible for a type of RDD. Furthermore, iPSC-based RPE therapy is expanded to include some clinical trials. Despite the incredible growth rate in iPSC-based studies on RPE-related diseases, there are some challenges, i.e., teratoma formation potential of iPSCs, an expensive procedure of iPSC-based regeneration of RPEs, lack of a universal protocol or cellular product applicable in all patients, etc. This article reviews the iPSC-based RPE generation and their therapeutic applications, studies on RPE-related molecular and cellular pathophysiologic features of RDD in the iPSC-based models, future perspectives, and the challenges ahead.