Age-Related Macular Degeneration: Therapeutic Strategies Based on Stem Cells

Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss among the elderly in developed countries, manifesting in two primary forms: neovascular (wet) AMD and non-neovascular (dry) AMD. Current treatments, such as anti-VEGF therapy, offer limited efficacy, particularly for dry AMD, highlighting the urgent need for alternative strategies. Advancements in contemporary treatment strategies for these eye conditions are a pressing medical concern. Stem cell-based therapies have emerged as a promising approach for retinal regeneration due to their capacity for self-renewal and differentiation into retinal cell types, including retinal pigment epithelial (RPE) cells and photoreceptors, two key cell populations damaged in AMD. Among the various sources, pluripotent stem cells such as human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) show significant potential in generating functional RPE cells and restoring retinal architecture and function. Preclinical and early clinical studies have demonstrated promising outcomes, including improved visual acuity and anatomical integration. However, challenges such as immune rejection, tumorigenicity, limited long-term integration, and ethical concerns continue to impede clinical translation. This review critically evaluates current stem cell-based therapeutic strategies for AMD, including advances in mesenchymal stem cells, retinal organoids, and combinatorial approaches with gene and nanotherapy. Furthermore, this review outlines the translational bottlenecks and future directions required to advance these therapies toward clinical application.