伴侣(临床)
视网膜病变
线粒体
医学
糖尿病性视网膜病变
生物信息学
细胞生物学
化学
生物
病理
内分泌学
糖尿病
作者
So‐Yeon Kim,Nam Gu Yoon,Jin Young Im,Ji Hye Lee,Juhee Kim,Yang Jeon,Young Jae Choi,Jong‐Hwa Lee,Akiyoshi Uemura,Dong Ho Park,Byoung Heon Kang
标识
DOI:10.1002/advs.202302776
摘要
Abstract Activation of hypoxia‐inducible factor 1α (HIF1α) contributes to blood‐retinal barrier (BRB) breakdown and pathological neovascularization responsible for vision loss in ischemic retinal diseases. During disease progression, mitochondrial biology is altered to adapt to the ischemic environment created by initial vascular dysfunction, but the mitochondrial adaptive mechanisms, which ultimately contribute to the pathogenesis of ischemic retinopathy, remain incompletely understood. In the present study, it is identified that expression of mitochondrial chaperone tumor necrosis factor receptor‐associated protein 1 (TRAP1) is essential for BRB breakdown and pathologic retinal neovascularization in mouse models mimicking ischemic retinopathies. Genetic Trap1 ablation or treatment with small molecule TRAP1 inhibitors, such as mitoquinone (MitoQ) and SB‐U015, alleviate retinal pathologies via proteolytic HIF1α degradation, which is mediated by opening of the mitochondrial permeability transition pore and activation of calcium‐dependent protease calpain‐1. These findings suggest that TRAP1 can be a promising target for the development of new treatments against ischemic retinopathy, such as retinopathy of prematurity and proliferative diabetic retinopathy.
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