Mechanism of blue light-induced ferroptosis in retinal pigment epithelium cells / 国际眼科杂志(Guoji Yanke Zazhi)

ABSTRACT

AIM: To investigate the occurrence and possible mechanism of blue light-induced ferroptosis in retinal pigment epithelial cells.METHODS: ARPE-19 cells cultured in vitro were irradiated by 405 nm blue light at 50 mW/cm2 irradiance with different duration and were divided into control, 16.3J/cm2, 32.6J/cm2, and 65.2J/cm2 groups; the 65.2J/cm2 group was defined as the high-level blue light irradiation group and cells were further divided into control, high-level blue light irradiation group and high-level blue light irradiation + ferroptosis inhibitor group. CCK-8 assay was used to detect cell viability, commercial kits were used to detect intracellular glutathione(GSH), ferrous iron and malondialdehyde(MDA)concentration, and Western blot was used to detect the relative expression of glutathione peroxidase 4(GPX4)and xCT proteins in cells.RESULTS: The decrease of ARPE-19 cell viability caused by blue light irradiation was dose-dependent, and the reduction of intracellular GSH concentration, the increase of ferrous iron concentration and MDA concentration were all caused by high-level blue light irradiation(all P<0.05); the ferroptosis inhibitor partially restored cell viability and recovered intracellular GSH, reduced concentrations of MDA and ferrous iron in the blue light irradiation group(all P<0.05). The relative expressions of GPX4 and xCT proteins were significantly decreased in the blue light irradiation group, and such change was alleviated by the ferroptosis inhibitor(P<0.05).CONCLUSION: Blue light irradiation may induce ferroptosis in RPE cells by targeting the xCT and GPX4-associated antioxidant pathways.