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.

The accumulation of the toxic byproduct A2E in retinal pigment epithelial cells, coupled with blue-light-induced photooxidation, is a key driver of oxidative damage in early age-related macular degeneration (AMD). Zeaxanthin dipalmitate (ZD), the esterified carotenoid abundant in goji berries, has higher lipophilicity and stability. In this study, ZD was isolated from the berries using its fat-soluble nature and purified using medium-pressure liquid chromatography. Isolated ZD and synthesised A2E were structurally characterised using HPLC, NMR, and positive mode LC-ESI-TQ-MS. An acellular photo-oxidation assay revealed that ZD significantly suppressed A2E degradation under blue light with higher efficacy than vitamin E, a standard antioxidant control. This indicates ZD's potent ability to filter blue light and scavenge reactive oxygen species, mitigating A2E photooxidation and phototoxicity. These findings highlight ZD's unique structural advantages for sustained retinal protection. The findings also support further in vivo and clinical studies of ZD as a natural photoprotective agent that targets early events in AMD.