Author:
Yagi Hitomi,Boeck Myriam,Nian Shen,Neilsen Katherine,Wang Chaomei,Lee Jeff,Zeng Yan,Grumbine Matthew,Sweet Ian R.,Kasai Taku,Negishi Kazuno,Singh Sasha A.,Aikawa Masanori,Hellström Ann,Smith Lois E. H.,Fu Zhongjie
Abstract
Abstract
Objective
Pathological 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.
Methods
OIR 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.
Results
In 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.
Conclusions
Mitochondrial energetics were suppressed during retinal NV in OIR. Appropriately timed supplementation of pyruvate may be a novel approach in neovascular retinal diseases.
Funder
National Institutes of Health
Kowa Company Ltd
National Institute of Health
Boston Children's Hospital
Mass Lions Eye Foundation
Publisher
Springer Science and Business Media LLC