Year: 2025
Type: article
Abstract: Dry age-related macular degeneration (AMD) is the leading cause of central vision loss among the elderly, yet no curative treatment exists. While exudative AMD can be managed with anti-vascular endothelial growth factor (VEGF) therapy, dry AMD-accounting for more than 85% of cases-progresses insidiously from drusen accumulation to geographic atrophy (GA). Although the recent U.S. Food and Drug Administration (FDA) approvals of pegcetacoplan and avacincaptad pegol represent major milestones, their therapeutic effects remain modest. This review provides an integrated overview of the molecular and cellular mechanisms underlying dry AMD, highlighting key pathogenic pathways involving oxidative stress, lipid dysregulation, complement activation, mitochondrial impairment, and RPE-specific bisretinoid lipofuscin accumulation. We further summarize mechanistic mouse models that replicate these pathological processes and discuss how each model contributes to understanding the disease. Finally, we review current and emerging therapeutic strategies-including complement inhibitors, visual cycle modulators, and mitochondrial-protective approaches-and outline future directions for translational research. Collectively, this review synthesizes mechanistic insights, disease models, and therapeutic innovation to support the development of targeted and stage-specific interventions for dry AMD.
DOI: 10.3390/ijms27010202
Authors: Shiva Kumar Bhandari, Sooyeun Lee, Hye Jin Kim
Institution: Keimyung University
Language: English
Subfield: Ophthalmology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,499
Funder: Keimyung University
OpenAlex ID: W7117128171