机构：[1]Eye Institute, Eye & ENT Hospital, Fudan University, Shanghai, China[2]NHC Key Laboratory of Myopia (Fudan University)[3]Key Laboratory of Myopia,Chinese Academy of Medical Sciences, Shanghai, China[3]Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, China[4]Beijing Instituteof Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing, China首都医科大学附属北京同仁医院首都医科大学附属同仁医院[5]Center for Biomedicine and Innovations, Faculty of Medicine, MacauUniversity of Science and Technology and University Hospital, Macau, China[6]Guangzhou KangRui Biological Pharmaceutical Technology Company,Guangzhou, China[7]Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China[8]Guangzhou Women and Children’sMedical Center, Guangzhou Medical University, Guangzhou, China[9]Department of Radiology, Eye & ENT Hospital, Fudan University, Shanghai, China[10]Center for Biomedical Imaging, Fudan University, Shanghai, China[11]State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for BrainScience, Fudan University, Shanghai, China[12]Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People’s Hospital,University of Electronic Science and Technology of China, Chengdu, Sichuan, China四川省人民医院[13]Guangzhou HuiBoRui Biological Pharmaceutical Technology Co., Ltd,Guangzhou, China
High myopia is a leading cause of blindness worldwide. Myopia progression may lead to pathological changes of lens and affect the outcome of lens surgery, but the underlying mechanism remains unclear. Here, we find an increased lens size in highly myopic eyes associated with up-regulation of β/γ-crystallin expressions. Similar findings are replicated in two independent mouse models of high myopia. Mechanistic studies show that the transcription factor MAF plays an essential role in up-regulating β/γ-crystallins in high myopia, by direct activation of the crystallin gene promoters and by activation of TGF-β1-Smad signaling. Our results establish lens morphological and molecular changes as a characteristic feature of high myopia, and point to the dysregulation of the MAF-TGF-β1-crystallin axis as an underlying mechanism, providing an insight for therapeutic interventions.
基金：
National Key Research and Development Program of
China (grant no. 2017YFC1104600), the National Natural Science Foundation of the
People’s Republic of China (grant nos. 81870642, 81470613, 81970780, and 81670835),
Shanghai High Myopia Study, Clinical Research Plan of SHDC (grant no.
SHDC2020CR4078), the Outstanding Youth Medical Talents Program of Shanghai
Health and Family Planning Commission (grant no. 2017YQ011), the Shanghai Talent
Development Fund (grant no. 201604), the Shanghai Youth Doctor Support Program
(grant no. 2014118), and the Recruitment Program of Leading Talents of Guangdong
Province (2016LJ06Y375).
第一作者机构：[1]Eye Institute, Eye & ENT Hospital, Fudan University, Shanghai, China[2]NHC Key Laboratory of Myopia (Fudan University)[3]Key Laboratory of Myopia,Chinese Academy of Medical Sciences, Shanghai, China[3]Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, China
共同第一作者：
通讯作者：
通讯机构：[1]Eye Institute, Eye & ENT Hospital, Fudan University, Shanghai, China[2]NHC Key Laboratory of Myopia (Fudan University)[3]Key Laboratory of Myopia,Chinese Academy of Medical Sciences, Shanghai, China[3]Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, China[5]Center for Biomedicine and Innovations, Faculty of Medicine, MacauUniversity of Science and Technology and University Hospital, Macau, China[8]Guangzhou Women and Children’sMedical Center, Guangzhou Medical University, Guangzhou, China[13]Guangzhou HuiBoRui Biological Pharmaceutical Technology Co., Ltd,Guangzhou, China
推荐引用方式(GB/T 7714)：
Xiangjia Zhu,Yu Du,Dan Li,et al.Aberrant TGF-β1 signaling activation by MAF underlies pathological lens growth in high myopia.[J].NATURE COMMUNICATIONS.2021,12(1):2102.doi:10.1038/s41467-021-22041-2.
APA：
Xiangjia Zhu,Yu Du,Dan Li,Jie Xu,Qingfeng Wu...&Yi Lu.(2021).Aberrant TGF-β1 signaling activation by MAF underlies pathological lens growth in high myopia..NATURE COMMUNICATIONS,12,(1)
MLA：
Xiangjia Zhu,et al."Aberrant TGF-β1 signaling activation by MAF underlies pathological lens growth in high myopia.".NATURE COMMUNICATIONS 12..1(2021):2102
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