Airborne fine particulate matter (PM2.5) damages the inner blood-retinal barrier by inducing inflammation and ferroptosis in retinal vascular endothelial cells
Airborne fine particulate matter (PM2.5) damages the inner blood-retinal barrier by inducing inflammation and ferroptosis in retinal vascular endothelial cells
复制标题
空气中的细颗粒物 (PM2.5) 通过诱导视网膜血管内皮细胞炎症和铁死亡来损害内部血-视网膜屏障
DOI：
10.1016/j.scitotenv.2022.156563
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发表时间：
2022-06-14
影响因子：
9.8
通讯作者：
Fu, Qiuli
中科院分区：
文献类型：
--
作者：
Gu, Yuzhou;Hao, Shengjie;Fu, Qiuli
这项研究首次探讨了空气中细颗粒物 (PM2.5) 暴露对内部血视网膜屏障 (iBRB) 的影响。在本研究中，暴露于PM2.5的动物模型（1 mg/mL PM2.5，每只眼10 μL，每天4次，3天）视网膜血管通透性和直径增加，同时可观察到视网膜水肿和视网膜炎症水平增加。 PM2.5 诱导的人视网膜微血管内皮细胞 (HRMEC) 细胞损伤以时间和剂量依赖性方式发生。观察到细胞活力、增殖、迁移和血管生成下降，以及细胞凋亡和炎症增加。 PM2.5暴露后（25、50和100μg/mL PM2.5持续24小时）也发现了铁过载和过度脂质氧化，以及铁死亡相关基因的表达显着改变，如前列腺素内过氧化物合酶2、谷胱甘肽过氧化物酶4和铁蛋白重链1。此外，铁死亡抑制剂Ferrostatin-1明显减轻了铁死亡相关基因的表达。 PM2.5 诱导的 HRMEC 细胞毒性。本研究调查了 PM2.5 对视网膜的体内影响，揭示 PM2.5 暴露会诱发视网膜炎症、血管扩张，并对 iBRB 造成损伤。在 PM2.5 诱导的 HRMEC 细胞毒性和功能障碍过程中发现了铁死亡的关键作用，这表明它是空气污染相关视网膜血管疾病的潜在预防目标。
This study was the first to explore the effect of airborne fine particulate matter (PM2.5) exposure on the inner blood-retinal barrier (iBRB). In this study, retinal vascular permeability and diameter were enhanced in the PM2.5-exposed animal model (1 mg/mL PM2.5, 10 mu L per eye, 4 times per day, 3 days), together with observable retinal edema and increased inflammation level in retina. PM2.5-induced cell damage in human retinal microvascular endothelial cells (HRMECs) occurred in a time- and dose-dependent manner. Decreased cell viability, proliferation, migration, and angiogenesis, as well as increased apoptosis and inflammation, were observed. Iron overload and excessive lipid oxidation were also discovered after PM2.5 exposure (25, 50, and 100 mu g/mL PM2.5 for 24 h), along with significantly altered expression of ferroptosis-related genes, such as prostaglandin-endoperoxide synthase 2, glutathione peroxidase 4, and ferritin heavy chain 1. Moreover, Ferrostatin-1, an inhibitor of ferroptosis, evidently alleviated the PM2.5-induced cytotoxicity of HRMECs. The present study investigated the in vivo effects of PM2.5 on retinas, revealing that PM2.5 exposure induced retinal inflammation, vascular dilatation, and caused damage to the iBRB. The crucial role of ferroptosis was discovered during PM2.5-induced HRMEC cytotoxicity and dysfunction, indicating a potential precautionary target in air pollution-associated retinal vascular diseases.