糖尿病性视网膜病变
脂质过氧化
视网膜
视网膜
活性氧
医学
视网膜病变
糖尿病
生物
内科学
氧化应激
细胞生物学
生物化学
内分泌学
神经科学
作者
Qun Li,Chaoqun Liu,Wan-Zhao Yi,Pei-Wen Ouyang,Bo-Fan Yang,Qi Ling,Jingmin Liu,Yongyan Wu,Aibin Liang,Yu‐Hong Cui,Jing Meng,Xiuyun Liu,Hongwei Pan
标识
DOI:10.1016/j.ajpath.2024.01.019
摘要
Ferroptosis is a new form of cell death characterized by iron-dependent lipid peroxidation. Whether ferroptosis is involved in retinal microvascular dysfunction under diabetic condition is not known. The expression of ferroptosis-related genes in patients with proliferative diabetic retinopathy and in diabetic mice was determined with RT-qPCR. Reactive oxygen species, iron content, lipid peroxidation products, and ferroptosis-associated proteins in the cultured human retinal microvascular endothelial cells (HRMECs) and in the retina of diabetic mice were examined. The association of ferroptosis with the functions of endothelial cells in vitro was evaluated. After administration of ferroptosis-specific inhibitor, Fer-1, the retinal microvasculature in diabetic mice was assessed. Characteristic changes of ferroptosis-associated markers, including GPX4, FTH1, long-chain acyl-CoA synthetase 4, TFRC, and cyclooxygenase-2, were detected in the retinal fibrovascular membrane of patients with proliferative diabetic retinopathy, cultured HRMECs, and the retina of diabetic mice. Elevated levels of reactive oxygen species, lipid peroxidation, and iron content were found in the retina of diabetic mice and in cultured HRMECs. Ferroptosis was found to be associated with HRMEC dysfunction under high-glucose condition. Inhibition of ferroptosis with specific inhibitor Fer-1 in diabetic mice significantly reduced the severity of retinal microvasculopathy. Ferroptosis contributes to microvascular dysfunction in diabetic retinopathy, and inhibition of ferroptosis might be a promising strategy for the therapy of early-stage diabetic retinopathy.
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