한빛사논문
- 조회485
So-Yeon Kim 1, Nam Gu Yoon 1, Jin Young Im 2, Ji Hye Lee 1, Juhee Kim 3 4, Yujin Jeon 3 4, Young Jae Choi 5, Jong-Hwa Lee 5 6, Akiyoshi Uemura 7, Dong Ho Park 3 4 *, Byoung Heon Kang 1 2 *
1Department of Biological Sciences, Ulsan National Institutes of Science and Technology (UNIST), Ulsan, 44919, Republic of Korea.
2SmartinBio Inc., Cheongju, 28160, Republic of Korea.
3Department of Ophthalmology, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, 41944, Republic of Korea.
4Cell & Matrix Research Institute, Kyungpook National University, Daegu, 41944, Republic of Korea.
5Bioanalysis and Pharmacokinetics Research Group, Korea Institute of Toxicology, Daejeon, 34114, Republic of Korea.
6Department of Human and Environment Toxicology, University of Science & Technology, Daejeon, 34113, Republic of Korea.
7Department of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, 467-8601, Japan.
†These authors contributed equally to this work
*Corresponding authors: correspondence to Dong Ho Park or Byoung Heon Kang
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.
논문정보
- Research article
- 2023년 11월 (BRIC 등록일 2023-11-21)
- 국내(교신)+국외 연구진
- 생명과학 > 생화학
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