Scleral hypoxia is a target for myopia control

作者：Hao Wu, Wei Chen, Fei Zhao, Qingyi Zhou, Peter S. Reinach, Lili Deng, Li Ma, Shumeng Luo, Nethrajeith Srinivasalu, Miaozhen Pan, Yang Hu, Xiaomeng Pei, Jing Sun, Ran Ren, Yinghui Xiong, Zhonglou Zhou, Sen Zhang, Geng Tian, Jianhuo Fang, Lina Zhang, Jidong Lang, Deng Wu, Changqing Zeng, Jia Qu, Xiangtian Zhou · 发表于：Proceedings of the National Academy of Sciences · 年份：2018 · DOI：10.1073/pnas.1721443115 · 被引用次数：527 · 研究领域：Glaucoma and retinal disorders、Corneal surgery and disorders、Ophthalmology and Visual Impairment Studies

) promoted myofibroblast transdifferentiation with down-regulation of type I collagen in human scleral fibroblasts. Importantly, the antihypoxia drugs salidroside and formononetin down-regulated HIF-1α expression as well as the phosphorylation levels of eIF2α and mTOR, slowing experimental myopia progression without affecting normal ocular growth in guinea pigs. Furthermore, eIF2α phosphorylation inhibition suppressed experimental myopia, whereas mTOR phosphorylation induced myopia in normal mice. Collectively, these findings defined an essential role of hypoxia in scleral ECM remodeling and myopia development, suggesting a therapeutic approach to control myopia by ameliorating hypoxia.