Gene and Stem Cell-Based Therapies for Retinal Degenerative Diseases: Update, Challenges, and Future Directions

Retinal degenerative diseases (RDDs) are a major global cause of irreversible vision loss, primarily resulting from the progressive degeneration of photoreceptors (PRs), retinal pigment epithelium (RPE), and retinal ganglion cells (RGCs). The limited regenerative capacity of the neural retina, combined with a lack of definitive therapies, highlights the urgent need for clinically viable strategies to slow degeneration or replace lost cells. While effective clinical treatments remain unavailable, recent advances in gene and stem cell therapies offer promising avenues to restore retinal structure and function. Preclinical and clinical studies have demonstrated encouraging safety and efficacy outcomes, supporting their potential to treat both inherited and acquired forms of RDDs. Nonetheless, several challenges-including vector limitations, immune responses, and delivery constraints-continue to hinder widespread clinical adoption. This review summarizes current gene and stem cell-based therapeutic strategies, recent clinical progress, and the key challenges and future directions shaping the evolving landscape of regenerative treatment for RDDs.