Blue light induced ferroptosis in retinal damage via iron overload-associated oxidative stress

The issue of light pollution has garnered increased attention recently, largely due to the widespread use of electronic devices. Blue light (BL) holds the highest energy level among visible light and has been extensively researched for its potential to cause damage to the retina. Ferroptosis, a recently identified form of programmed cell death form, has been linked to retinal diseases. However, the connection between BL-induced retinal damage and ferroptosis remains elusive. This study aims to investigate the involvement of ferroptosis in retinal damage under BL exposure and its underlying mechanism. In this study, a mouse retinal damage model and cultured ARPE-19 cells exposed to BL were employed. Various techniques including Haematoxylin-eosin staining, fundus photography, immunostaining, and transmission electron microscopy were employed to examine retinal structure and morphology changes resulting from BL exposure. To identify ferroptosis levels in vitro, we employed DCFH-DA, C11-BODIPY 581/591, and FeRhoNox™-1 probes. Additionally, real-time PCR and western blotting techniques were used to uncover potential targets in BL-induced ferroptosis. Our study showed that BL exposure can result in iron overload, oxidative stress, evidenced by increased markers TFR1, ACSL4, HO-1 and decreased expression level of SOD2, CAT and ferroptosis-associated gene of GPX4. Interestingly, we found that Deferoxamine mesylate, a compound capable of chelating excess Fe²⁺ caused by BL, effectively mitigated lipid peroxidation, and alleviated retinal damage both in vivo and in vitro. The discoveries will advance our knowledge of BL-induced retinal damage.