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Cheng Li, Fei Dong, Wei Li, Zuguo Liu; Notch Inhibitor DAPT Blocks Fibroblastic Transformation of Corneal Endothelium. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6007.
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To explore the role of Notch signaling in corneal endothelial-mesenchymal transformation (EnMT).
EnMT was induced in rat corneal endothelial cells (RCECs) by serial passages or TGF-β treatment, with or without 10µM DAPT. Cell phenotype and transformation were evaluated by EnMT markers, growth curve, scratch test, immunostaining and RT-qPCR. An in vivo EnMT rat model was induced by transcorneal freezing, with or without topical treatment of 50µM DAPT for 14 days. The wound endothelium was evaluated by slit lamp, stereomicroscope, immunostaining and RT-qPCR.
Corneal EnMT in vitro was evidenced by changed morphology, downregulated tight junctions (ZO-1, Cx43 and N-cadherin), increased α-SMA and Notch signaling (Notch1, Notch2, Jag1 and Hes1). DAPT blocked EnMT induction, also reversed the phenotype, morphology and hyperplasia of the transformed RCECs. In rat, DAPT treatment blocked the EnMT process, with normal tight junction and suppressed α-SMA and Notch signaling, and no retrocorneal membrane formed.
It was indentified for the first time that Notch signaling is a novel therapeutic target for corneal endothelial fibrogenic disorders.
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