Antioxidant Strategies for Inherited Retinal Degenerations in the Era of Gene Therapy

Inherited retinal degenerations (IRDs) are a genetically heterogeneous group of disorders characterized by progressive loss of photoreceptors and retinal pigment epithelium, leading to irreversible vision impairment. Although gene therapy has transformed the therapeutic outlook for IRDs, its efficacy remains limited by gene and variant specificity, a narrow treatment window dependent on viable target cells, and the persistence of retinal degeneration even after restoration of gene function. In this review, we summarize current gene-based therapeutic strategies, critically examine oxidative stress as a shared but heterogeneous downstream mechanism across IRDs, and review antioxidant and redox-modulating interventions with particular emphasis on the distinction between preclinical and clinical evidence. This review highlights that oxidative stress contributes to inflammation, metabolic dysfunction, and cellular damage during disease progression and may be exacerbated by interventions associated with gene therapy—including vector-induced immune activation, transgene-related cellular stress, and delivery-associated tissue injury. However, direct evidence supporting antioxidant–gene therapy combinations remains predominantly preclinical, and their clinical efficacy has not yet been established. Disease- and stage-specific integration of antioxidants and redox modulation may help preserve viable retinal cells, support retinal homeostasis during genetic rescue, and potentially improve treatment durability.