视网膜能量代谢的Warburg效应及其调控机制

Warburg effect of retinal energetic metabolism and its regulatory mechanism

视网膜的代谢过程包括物质代谢和能量代谢,视网膜是人体高耗能的神经组织,故维持其能量代谢过程的稳态对于视网膜正常功能的维持极其重要。视网膜能量代谢特征与生长非常快速的肿瘤组织类似,即在有氧情况下主要依赖糖酵解途径供能,称为视网膜Warburg效应。视网膜能量代谢的Warburg效应重要意义在于,相比于氧化磷酸化途径,葡萄糖可以迅速通过糖酵解途径产生ATP,并可为快速增生的细胞的生物合成过程供给所需的碳源。视网膜的代谢能量是视网膜中各种细胞代谢活动产能的总和,涉及光感受器细胞、色素上皮细胞、Müller细胞以及视网膜血管内皮细胞等,研究这些细胞产生Warburg效应的原因及细胞间代谢偶联的机制对了解视网膜能量代谢活动的过程非常重要。作为糖酵解途径的关键酶,HK2、PFKFB3和PKM2活性及其表达水平的变化与细胞增生和新生血管的生成有着密切的关联,深入研究这些机制有望为年龄相关性黄斑变性(AMD)等视网膜能量代谢障碍疾病的治疗提供新的思路。本文就视网膜能量代谢的Warburg效应及其调控机制进行综述。

Retinal metabolism includes material metabolism and energetic metabolism.Retina is one of the most energy-consuming nerve tissue in human body and mainly relies on glycolysis for energy production,which is similar to very fast-growing tumor tissue.This process is known as Warburg effect.Warburg effect is of great significance,which is demonstrated that glucose is metabolized via glycolysis in a more rapid approach in comparison with oxidative phosphorylation pathway.In addition,glucose also supplies neoplastic tissue with carbon source or metabolic intermediates due to biosynthesis.The produced energy of retina is a summation of different retinal cells and tissue,such as photoreceptors,retinal pigment epithelium(RPE),Müller cells and retinal capillary endothelial cells etc.To understand the underlying mechanism contributing to Warburg effect and provide insight into metabolic coupling between neuron and glia is of important significance.Since key glycolysis enzymes(HK2,PFKFB3 and PKM2)take a pivotal role in controlling retinal cell proliferation and neovascularization,bioenergetic strategy targeting these enzymes suggests new idea in the treatment of retinal diseases where energy failure is part of the pathogenesis.Investigating underlying mechanism of retinal energy metabolism can provide new ideas for the treatment of age-related macular degeneration(AMD)and other diseases related to disordered retinal energy metabolism.The Warburg effect of retinal energetic metabolism and its regulatory mechanism were reviewed in this article.