小柯机器人

温州医科大学赵斐等研究人员合作发现，巩膜糖酵解的增强通过组蛋白乳酸化增强促进近视的形成。2024年1月16日，国际知名学术期刊《细胞—代谢》在线发表了这一成果。

研究人员发现小鼠和豚鼠的近视与缺氧诱导的巩膜中关键糖酵解酶表达和乳酸水平的增加有关。促进巩膜糖酵解或乳酸盐生成可诱导巩膜成纤维细胞向肌成纤维细胞转分化（FMT）和近视；相反，抑制糖酵解或乳酸盐生成则可消除或抑制FMT和近视。从机理上讲，巩膜糖酵解-乳酸盐水平的增加通过H3K18la促进了FMT和近视的发生，而这又促进了Notch1的表达。遗传分析发现，两个编码糖酵解酶的基因ENO2和TPI1显著富集。

此外，增加豚鼠的糖摄入量不仅能诱导近视，还能通过巩膜糖酵解-乳酸-组蛋白乳酸化途径增强对近视诱导的反应。总之，研究人员认为巩膜糖酵解通过乳酸诱导的组蛋白乳酸化促进FMT，从而导致近视。

研究人员表示，近视的特点是FMT的不适应性增加。巩膜缺氧是导致近视的一个重要因素，但人们对缺氧如何诱发近视却知之甚少。

附：英文原文

Title: Augmentation of scleral glycolysis promotes myopia through histone lactylation

Author: Xiaolei Lin, Yi Lei, Miaozhen Pan, Changxi Hu, Bintao Xie, Wenjing Wu, Jianzhong Su, Yating Li, Yuhan Tan, Xiaohuan Wei, Zhengbo Xue, Ruiyan Xu, Mengqi Di, Hanyu Deng, Shengcong Liu, Xingxing Yang, Jia Qu, Wei Chen, Xiangtian Zhou, Fei Zhao

Issue&Volume: 2024-01-16

Abstract: Myopia is characterized of maladaptive increases in scleral fibroblast-to-myofibroblasttransdifferentiation (FMT). Scleral hypoxia is a significant factor contributing tomyopia, but how hypoxia induces myopia is poorly understood. Here, we showed thatmyopia in mice and guinea pigs was associated with hypoxia-induced increases in keyglycolytic enzymes expression and lactate levels in the sclera. Promotion of scleralglycolysis or lactate production induced FMT and myopia; conversely, suppression ofglycolysis or lactate production eliminated or inhibited FMT and myopia. Mechanistically,increasing scleral glycolysis-lactate levels promoted FMT and myopia via H3K18la,and this promoted Notch1 expression. Genetic analyses identified a significant enrichment of two genes encodingglycolytic enzymes, ENO2 and TPI1. Moreover, increasing sugar intake in guinea pigs not only induced myopia but alsoenhanced the response to myopia induction via the scleral glycolysis-lactate-histonelactylation pathway. Collectively, we suggest that scleral glycolysis contributesto myopia by promoting FMT via lactate-induced histone lactylation.

DOI: 10.1016/j.cmet.2023.12.023

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(23)00474-6

Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
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