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.
方法:在C57BL/6J小鼠中诱导OIR,并在最大新血管形成时检查视网膜脉管系统。我们评估了OIR的总蛋白质组变化以及线粒体与核DNA拷贝数(mtDNA/nDNA)之比控制视网膜,和离体OIR中的线粒体耗氧率(OCR)与控制视网膜(BaroFuse)。丙酮酸与在新血管形成之前或期间向OIR小鼠补充媒介物对照。
结果:在OIR与控制视网膜,全球蛋白质组学显示,在新生血管形成高峰时,视网膜线粒体呼吸减少。OCR和mtDNA/nDNA在新血管形成高峰时也降低,表明线粒体呼吸受损。在新血管形成过程中但不是在新血管形成之前(与线粒体活性时程一致)的体内丙酮酸给药抑制了NV。
结论:OIR中视网膜NV时线粒体能量被抑制。适当定时补充丙酮酸可能是新生血管性视网膜疾病的一种新方法。