The dysfunction and cell death of retinal pigment epithelial (RPE) cells are hallmarks of late-stage dry (atrophic) age-related macular degeneration (AMD), for which no effective therapy has yet been developed. Previous studies have indicated that iron accumulation is a source of excess free radical production in RPE, and age-dependent iron accumulation in RPE is accelerated in patients with dry AMD. Although the pathogenic role of oxidative stress in RPE in the development of dry AMD is widely accepted, the mechanisms of oxidative stress-induced RPE cell death remain elusive. Here, we show that ferroptotic cell death, a mode of regulated necrosis mediated by iron and lipid peroxidation, is implicated in oxidative stress-induced RPE cell death in vitro. In ARPE-19 cells we observed that the ferroptosis inhibitors ferrostatin-1 and deferoxamine (DFO) rescued tert-butyl hydroperoxide (tBH)-induced RPE cell death more effectively than inhibitors of apoptosis or necroptosis. tBH-induced RPE cell death was accompanied by the three characteristics of ferroptotic cell death: lipid peroxidation, glutathione depletion, and ferrous iron accumulation, which were all significantly attenuated by ferrostatin-1 and DFO. Exogenous iron overload enhanced tBH-induced RPE cell death, but this effect was also attenuated by ferrostatin-1 and DFO. Furthermore, mRNA levels of numerous genes known to regulate iron metabolism were observed to be influenced by oxidative stress. Taken together, our observations suggest that multiple modes of cell death are involved in oxidative stress-induced RPE cell death, with ferroptosis playing a particularly important role.

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Background factors and ophthalmic findings are similar to those that have been reported previously, including relatively stable findings even after a long observation and the occurrence of central serous chorioretinopathy and choroidal neovascularization. Bilateral cases are not rare in the current cohort, and choroidal vascular hyperpermeability is frequently observed in indocyanine green angiography, suggesting there were choroidal hemodynamic changes around the excavation.

Background:The essentiality of an antioxidant enzyme for the development and maturation of photoreceptor cells has remained unclear. Results: While GPx4-abrogated photoreceptor cells develop and differentiate into rod and cone cells, their outer segments are structurally disorganized and they undergo rapid apoptosis in vivo. Conclusion: GPx4 is essential for the maturation of photoreceptor cells. Significance: A novel role of an antioxidant enzyme for photoreceptor cells is disclosed in this study.

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This microsurgical system that we have developed has superior operability as compared to traditional manual procedure and has sufficient potential to be used clinically for vitreoretinal surgery.

Currently available evidence in the literature indicates that additional ILM peeling in vitrectomy for idiopathic ERM could result in a significantly lower ERM recurrence rate, but it does not significantly influence postoperative best-corrected visual acuity and central macular thickness.

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