Stem cell–based therapies for inherited retinal diseases – Translational advances and clinical evidence: A review

Abstract

Inherited retinal diseases (IRDs) represent a genetically diverse group of disorders that result in the progressive degeneration of photoreceptors and/or retinal pigment epithelium (RPE), ultimately leading to significant vision loss and diminished quality of life. Symptoms vary widely, encompassing night blindness, peripheral vision loss, central vision impairment, and total blindness, with disease progression influenced by the specific genetic mutation and inheritance pattern. This narrative review synthesizes recent findings on the pathogenesis of IRDs and examines stem cell-based interventions across preclinical models and early clinical trials. Mutations in genes such as RPE65, ABCA4, and USH2A disrupt critical retinal pathways, contributing to oxidative stress, inflammation, and apoptosis. Stem cell strategies, including pluripotent stem cell-derived RPE/photoreceptor precursors, mesenchymal stem cells, and retinal progenitor cells, offer potential mechanisms for limited cellular replacement and synaptic integration, as well as paracrine neuroprotection and immunomodulation. Current research indicates feasible delivery methods (intravitreal, subretinal, or suprachoroidal) with generally acceptable safety profiles; however, functional improvements in vision are often inconsistent and temporary, and durable vision restoration remains unproven. Significant challenges persist, including immune rejection, tumorigenicity risks, weak engraftment, technical complexity, and regulatory barriers. These issues underscore the necessity for standardized manufacturing processes and well-controlled, long-term clinical trials to advance the field of IRD treatment.