Academic Journal
Targeting the Mitochondrial Chaperone TRAP1 Alleviates Vascular Pathologies in Ischemic Retinopathy
| العنوان: | Targeting the Mitochondrial Chaperone TRAP1 Alleviates Vascular Pathologies in Ischemic Retinopathy |
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| المؤلفون: | Kim, So‐Yeon, Yoon, Nam Gu, Im, Jin Young, Lee, Ji Hye, Kim, Juhee, Jeon, Yujin, Choi, Young Jae, Lee, Jong‐Hwa, Uemura, Akiyoshi, Park, Dong Ho, Kang, Byoung Heon |
| المساهمون: | National Research Foundation of Korea, Korea Drug Development Fund, Ministry of Health and Welfare, Institute for Information and communications Technology Promotion |
| المصدر: | Advanced Science ; volume 11, issue 2 ; ISSN 2198-3844 2198-3844 |
| بيانات النشر: | Wiley |
| سنة النشر: | 2023 |
| المجموعة: | Wiley Online Library (Open Access Articles via Crossref) |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1002/advs.202302776 |
| الاتاحة: | http://dx.doi.org/10.1002/advs.202302776 https://onlinelibrary.wiley.com/doi/pdf/10.1002/advs.202302776 |
| Rights: | http://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: | edsbas.A4196351 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1002/advs.202302776 |
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