Retinitis Pigmentosa: A Review of Its Pathogenesis and Emerging Molecular and Cellular Therapies

Abstract

Retinitis pigmentosa (RP) is the most common inherited retinal dystrophy and remains largely untreatable. This review summarizes RP pathogenesis and critically appraises emerging therapeutic strategies, including gene augmentation, gene editing, RNA-based therapies, gene-agnostic and neuroprotective approaches, stem-cell therapy and their delivery platforms. We compare these strategies according to mutation mechanism, disease stage, durability, delivery route, and current level of clinical evidence. Although several approaches have shown improved structural and functional outcomes in preclinical and early-phase studies, RPE65-directed gene augmentation (voretigen neparvovec) remains the only approved therapy, and even it does not halt degeneration. For most modalities, long-term efficacy, safety, durability and clinical validation are not yet established, and translation is further constrained by delivery, immunogenicity, manufacturing, and cost. Rather than a realized paradigm shift, current evidence points to a rapidly advancing but still largely investigational field with successful clinical translation remaining elusive.