Advancements in age-related macular degeneration treatment: From traditional anti-VEGF to emerging therapies in gene, stem cell, and nanotechnology

Abstract

Age-related macular degeneration (AMD) is the leading cause of central vision loss in older adults and is projected to affect approximately 400 million individuals worldwide by 2040. Its pathological characteristics include retinal extracellular deposits, such as drusen, which trigger photoreceptor degeneration and damage to the retinal pigment epithelium (RPE), resulting in irreversible vision loss. The pathogenesis of AMD involves genetic, environmental, and aging-related factors. Anti-vascular endothelial growth factor (anti-VEGF) therapy for wet AMD significantly inhibits choroidal neovascularization and delays visual deterioration. However, its high cost, frequent injections, and poor patient compliance limit application, and there remains no effective intervention for dry AMD. In recent years, emerging strategies, such as gene therapy, stem cell therapy, and nanotechnology-based drug delivery systems, offer hope for slowing disease progression by improving targeting, drug stability, and reducing treatment frequency. Nanoparticles, including polymeric and lipid systems, have shown promise for enhancing drug delivery and bioavailability, particularly for dry AMD, where existing therapies are inadequate. These strategies also have the potential to improve patient compliance. This review summarizes AMD epidemiology and examines the limitations of current therapies. It emphasizes the mechanisms and clinical advancements of gene therapy, stem cell therapy, and nanotechnology in AMD treatment. These emerging technologies offer promising opportunities for precision medicine and lay a solid foundation for the future development of multifaceted therapeutic strategies.

Keywords: Age-related macular degeneration; Anti-vascular endothelial growth factor; Gene therapy; Nanotechnology-based drug delivery; Stem cell therapy.