Blue LED light induces dry eye disease via NCOA4-mediated ferritinophagy and iron-overload

Purpose: To explore how blue light-emitting diode (LED) exposure affects ferritinophagy and iron homeostasis in the conjunctival epithelium. Methods: C57BL/6 J mice and human conjunctival epithelial cells were exposed to blue LED light. Ocular surface changes were assessed via TBUT, corneal fluorescein staining. Ferroptosis was evaluated by TEM, H&E staining, immunofluorescence, CCK-8 assays, and fluorescence probes (FeRhoNox™, Calcein-AM, C11-BODIPY). NCOA4 siRNA and the inhibitor NCOA4–9a were used to investigate ferritinophagy's role. Results: Blue LED light caused significant iron accumulation and ferroptosis-like injury in the conjunctival epithelium. Deferiprone treatment mitigated iron overload, preserved epithelial morphology, and improved dry eye symptoms. In vitro, DFP restored intracellular iron balance and suppressed lipid peroxidation. Mechanistically, blue light triggered NCOA4-mediated ferritinophagy, disrupting iron homeostasis and driving ferroptosis. NCOA4–9a eye drops alleviated ferroptosis damage and dry eye symptoms in vivo. Conclusion: Blue LED exposure induces dry eye and conjunctival epithelial injury via NCOA4-dependent ferritinophagy and ferroptosis. Modulating iron metabolism through DFP or NCOA4–9a represents a promising therapeutic approach for LED-associated ocular surface diseases.