Application of Subretinal Stem Cell Transplantation in the Treatment of Wet Age-Related Macular Degeneration: Current Approaches and Future Perspectives

Abstract

Wet age-related macular degeneration (wAMD) is a leading cause of vision loss among the elderly, characterized by choroidal neovascularization (CNV) and retinal damage. Current treatments, such as anti-vascular epithelial growth factor (VEGF) therapies, offer symptomatic relief but do not restore lost retinal tissues or address the underlying degenerative processes. Subretinal stem cell transplantation has emerged as a promising therapeutic strategy aimed at regenerating damaged retinal cells, particularly the retinal pigment epithelium (RPE), to promote retinal repair. This review provides an overview of the pathophysiology of wAMD, highlighting the critical roles of RPE dysfunction and pathological vascular changes. It explores various stem cell types, including embryonic stem cells, induced pluripotent stem cells, and mesenchymal stem cells, which show potentials for retinal regeneration. The scientific rationale behind subretinal transplantation is discussed, along with advancements in cell differentiation protocols, surgical techniques, and biomaterial-assisted delivery systems. Recent preclinical and clinical studies are examined, demonstrating the feasibility and safety of stem cell transplantation, although challenges remain regarding cell survival, integration, and immune rejection. Emerging technologies, such as gene editing and combination therapies, are also reviewed for their potential to enhance therapeutic outcomes. This comprehensive analysis highlights the future potential of subretinal stem cell transplantation as a disease-modifying approach for wAMD.