Altered Energy Metabolism During Early Optic Nerve Crush Injury:Implications of Warburg-Like Aerobic Glycolysis in Facilitating Retinal Ganglion Cell Survival

作     者：Jingyi Zhu Ping Li Yuan-Guo Zhou Jian Ye Jingyi Zhu;Ping Li;Yuan-Guo Zhou;Jian Ye

作者机构：Department of OphthalmologyArmy Medical Center of the People's Liberation Army(PLA)Army Medical UniversityChongqing 400042China Molecular Biology CenterState Key Laboratory of TraumaBumand Combined InjuryResearch Institute of SurgeryArmy Medical Center of the PLAArmy Medical UniversityChongqing 400042China 

出 版 物：《Neuroscience Bulletin》 (神经科学通报（英文版）)

年 卷 期：2020年第36卷第7期

页      面：761-777页

核心收录：

学科分类：1002[医学-临床医学] 100212[医学-眼科学] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China (81371006) 

主　　题：Optic nerve crush ATP Glycolysis Oxidative phosphorylation RGC survival 

摘      要：Neurons,especially axons,are metabolically demanding and energetically vulnerable during ***,the exact energy budget alterations that occur early after axon injury and the effects of these changes on neuronal survival remain *** a classic mouse model of optic nerve-crush injury,we found that traumatized optic nerves and retinas harbor the potential to mobilize two primary energetic machineries,glycolysis and oxidative phosphorylation,to satisfy the robustly increased adenosine triphosphate(ATP) *** exploration of metabolic activation showed that mitochondrial oxidative phosphorylation was amplified over other pathways,which may lead to decreased retinal ganglion cell(RGC) survival despite its supplement to ATP *** set enrichment analysis of a microarray(GSE32309) identified significant activation of oxidative phosphorylation in injured retinas from wild-type mice compared to those from mice with deletion of phosphatase and tensin homolog(PTEN),while PTEN-/-mice had more robust RGC ***,we speculated that the oxidation-favoring metabolic pattern after optic nervecrush injury could be adverse for RGC *** redirecting metabolic flux toward glycolysis(magnifying the Warburg effect) using the drug meclizine,we successfully increased RGC ***,we provide novel insights into a potential bioenergetics-based strategy for neuroprotection.