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.