Mitochondrial control of hypoxia-induced pathological retinal angiogenesis (Aug, 10.1007/s10456-024-09940-w, 2024)

被引：0

作者：

Yagi, Hitomi ^{[1
,2
]}

Boeck, Myriam ^{[1
,3
]}

Nian, Shen ^{[1
,4
]}

Neilsen, Katherine ^{[1
]}

Wang, Chaomei ^{[1
]}

Lee, Jeff ^{[1
]}

Zeng, Yan ^{[1
]}

Grumbine, Matthew ^{[5
]}

Sweet, Ian R. ^{[6
]}

Kasai, Taku ^{[7
]}

Negishi, Kazuno ^{[2
]}

Singh, Sasha A. ^{[7
]}

Aikawa, Masanori ^{[7
,8
,9
]}

Hellstroem, Ann ^{[10
]}

Smith, Lois E. H. ^{[1
]}

Fu, Zhongjie ^{[1
]}

机构：

[1] Harvard Med Sch, Boston Childrens Hosp, Dept Ophthalmol, 3 Blackfan Circle,CLS 18, Boston, MA 02115 USA

[2] Keio Univ, Sch Med, Dept Ophthalmol, Tokyo 1608582, Japan

[3] Univ Freiburg, Fac Med, Eye Ctr, Med Ctr, D-79106 Freiburg, Germany

[4] Xian Med Univ, Dept Pathol, Xian 710021, Shaanxi, Peoples R China

[5] EnTox Sci Inc, Mercer Isl, WA 98040 USA

[6] Univ Washington, Med Diabet Inst, Seattle, WA 98109 USA

[7] Harvard Med Sch, Brigham Womens Hosp, Ctr Interdisciplinary Cardiovasc Sci, Dept Med,Div Cardiovasc Med, Boston, MA 02115 USA

[8] Harvard Med Sch, Brigham & Womens Hosp, Ctr Excellence Vasc Biol, Div Cardiovasc Med, Boston, MA 02115 USA

[9] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA

[10] Univ Gothenburg, Inst Neurosci & Physiol, Sahlgrenska Acad, Sahlgrenska Ctr Pediat Ophthalmol Res,Dept Clin Ne, S-40530 Gothenburg, Sweden

来源：

ANGIOGENESIS | 2024年 / 27卷 / 04期

基金：

美国国家卫生研究院;

关键词：

Hypoxia; Mitochondrial respiration; Neovascularization; Oxygen-induced retinopathy; Retinal angiogenesis; Retinopathy of prematurity;

D O I：

10.1007/s10456-024-09952-6

中图分类号：

R6 [外科学];

学科分类号：

1002 ; 100210 ;

摘要：

ObjectivePathological retinal neovascularization is vision-threatening. In mouse oxygen-induced retinopathy (OIR) we sought to define mitochondrial respiration changes longitudinally during hyperoxia-induced vessel loss and hypoxia-induced neovascularization, and to test interventions addressing those changes to prevent neovascularization.MethodsOIR was induced in C57BL/6J mice and retinal vasculature was examined at maximum neovessel formation. We assessed total proteome changes and the ratio of mitochondrial to nuclear DNA copy numbers (mtDNA/nDNA) of OIR vs. control retinas, and mitochondrial oxygen consumption rates (OCR) in ex vivo OIR vs. control retinas (BaroFuse). Pyruvate vs. vehicle control was supplemented to OIR mice either prior to or during neovessel formation.ResultsIn OIR vs. control retinas, global proteomics showed decreased retinal mitochondrial respiration at peak neovascularization. OCR and mtDNA/nDNA were also decreased at peak neovascularization suggesting impaired mitochondrial respiration. In vivo pyruvate administration during but not prior to neovessel formation (in line with mitochondrial activity time course) suppressed NV.ConclusionsMitochondrial energetics were suppressed during retinal NV in OIR. Appropriately timed supplementation of pyruvate may be a novel approach in neovascular retinal diseases.

引用

页码：701 / 702

页数：2