Aberrant TGF-β1 signaling activation by MAF underlies pathological lens growth in high myopia.

Xiangjia Zhu, Yu Du, Dan Li, Jie Xu, Qingfeng Wu, Wenwen He, Keke Zhang, Jie Zhu, Linying Guo, Ming Qi, Ailin Liu, Jiao Qi, Guangyu Wang, Jiaqi Meng, Zhenglin Yang, Kang Zhang, Yi Lu

Nature communications 2021 Apr 08

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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.

Citation

Xiangjia Zhu, Yu Du, Dan Li, Jie Xu, Qingfeng Wu, Wenwen He, Keke Zhang, Jie Zhu, Linying Guo, Ming Qi, Ailin Liu, Jiao Qi, Guangyu Wang, Jiaqi Meng, Zhenglin Yang, Kang Zhang, Yi Lu. Aberrant TGF-β1 signaling activation by MAF underlies pathological lens growth in high myopia. Nature communications. 2021 Apr 08;12(1):2102