Eye Institute and Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai, China; Key Laboratory of Visual Impairment and Restoration, Fudan University, Shanghai, China; Key Laboratory of Myopia (Fudan University), Chinese Academy of Medical Sciences, National Health Commission, Shanghai, China.
Eye Institute and Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai, China; Key Laboratory of Visual Impairment and Restoration, Fudan University, Shanghai, China; Key Laboratory of Myopia (Fudan University), Chinese Academy of Medical Sciences, National Health Commission, Shanghai, China.
Biochem Biophys Res Commun. 2021 Apr 9;548:27-34. doi: 10.1016/j.bbrc.2021.02.055. Epub 2021 Feb 22.
Degenerative retinal diseases, including age-related macular degeneration, are serious diseases that may lead to irreversible retinal neuron damage and permanent vision impairment. There are currently no effective treatments for these diseases due to our incomplete understanding of the underlying pathological mechanisms. Ferroptosis, a newly identified iron-dependent mode of cell death, is implicated in various diseases. However, it is unknown whether ferroptosis is involved in light-induced retinal degeneration. In this study, we found that light exposure significantly reduced the viability of photoreceptor cells in vitro and induced pro-ferroptotic changes, including iron accumulation, mitochondrial shrinkage, glutathione depletion, increased malondialdehyde (MDA), and decreased protein expression of SLC7A11 and GPX4. The effects of light exposure on ferroptosis were attenuated by ferrostatin-1. Consistently, the results of in vivo studies demonstrated that ferrostatin-1 protected against light-induced ferroptosis. And it exerted therapeutic effects by inhibiting neuroinflammation and prevented the effects of light exposure on the structure and function of the retina. The findings reveal an important role of ferroptosis in the pathogenesis of light-induced retinal degeneration and suggest that ferroptosis may be a novel treatment target for preventing retinal degeneration.
退行性视网膜疾病，包括年龄相关性黄斑变性，是严重的疾病，可能导致不可逆转的视网膜神经元损伤和永久性视力损害。由于我们对潜在病理机制的不完全了解，目前这些疾病还没有有效的治疗方法。铁死亡，一种新发现的铁依赖性细胞死亡方式，与各种疾病有关。然而，铁死亡是否参与光诱导的视网膜变性尚不清楚。在这项研究中，我们发现光暴露显著降低了体外感光细胞的活力，并诱导了促铁死亡的变化，包括铁积累、线粒体收缩、谷胱甘肽耗竭、丙二醛（MDA）增加和 SLC7A11 和 GPX4 蛋白表达减少。铁死亡抑制剂 ferrostatin-1 可减轻光暴露对铁死亡的影响。同样，体内研究结果表明，ferrostatin-1 可预防光诱导的铁死亡，并通过抑制神经炎症来发挥治疗作用，防止光暴露对视网膜结构和功能的影响。这些发现揭示了铁死亡在光诱导的视网膜变性发病机制中的重要作用，并表明铁死亡可能是预防视网膜变性的一种新的治疗靶点。
