Blue light pollution causes retinal damage and degeneration by inducing ferroptosis

With the development of technology and electronic products, the problem of light pollution is becoming more and more serious. Blue light, the most energetic light in visible light, is the main culprit of teenage vision problems in the modern environment. As the tissue with the highest oxygen consumption, the retina is vulnerable to oxidative stress. However, the exact way in which blue light-triggered reactive oxygen species (ROS) cause retinal cell death remains unclear. Ferroptosis is a newly defined cell death pathway, whose core molecular mechanism is cell death caused by excessive lipid peroxidation. In this study, the results indicated that blue light-triggered ROS burst in retinal cells, in the meantime, intracellular Fe²⁺ levels were also significantly up-regulated. Further, deferoxamine (DFO) significantly improved blue light-triggered lipid peroxidation and cell death in ARPE-19 cells, and ferrostatin-1 (Fer-1) alleviated retinal oxidative stress and degeneration in rats. Furthermore, the GSH-GPX4 and FSP1-CoQ₁₀-NADH systems served as key systems for cellular defense against ferroptosis, and interestingly, our results demonstrated that blue light triggered imbalance of the GSH-GPX4 and FSP1-CoQ₁₀-NADH systems in retinal cells. Taken together, these pieces of evidence suggest that ferroptosis may be a crucial pathway for blue light-induced retinal damage and degeneration, which helps us to understand exactly why blue light pollution causes visual impairment in adolescents.