Cell Death Dis. 2025 Oct 6;16(1):692. doi: 10.1038/s41419-025-07950-0.
ABSTRACT
Dysregulation of iron homeostasis plays a crucial role in retinal diseases, contributing to oxidative stress, inflammation, and ferroptosis, key processes that drive the degeneration of the retinal pigment epithelium (RPE) and photoreceptors in age-related macular degeneration (AMD). Previous studies, though limited in patient numbers, have reported elevated iron levels in the aqueous humor, RPE, and Bruch’s membrane of AMD patients. In this study, we aimed to confirm iron imbalance in a larger cohort of AMD patients and assess its correlation with disease stage. Elevated iron levels and a reduction in transferrin (TF) iron-binding capacity were observed in patients with early geographic atrophy (GA). RPE cells derived from human stem cells exhibited AMD-like features when exposed to iron overload or oxidized lipids. Treatment with TF appeared to restore aspects of iron homeostasis and reduce oxidative stress, mitochondrial damage, inflammation, complement activation, and ferroptosis in this model. These findings suggest that TF supplementation may represent a potential therapeutic strategy to help prevent or slow AMD progression.
PMID:41053100 | DOI:10.1038/s41419-025-07950-0