March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
Notch Inhibitor DAPT Blocks Fibroblastic Transformation of Corneal Endothelium
Author Affiliations & Notes
  • Cheng Li
    Eye Inst & Affiliated Xiamen Eye Ctr, Xiamen, China
  • Fei Dong
    Eye Inst & Affiliated Xiamen Eye Ctr, Xiamen, China
  • Wei Li
    Eye Inst & Affiliated Xiamen Eye Ctr, Xiamen, China
  • Zuguo Liu
    Eye Inst & Affiliated Xiamen Eye Ctr, Xiamen, China
  • Footnotes
    Commercial Relationships  Cheng Li, None; Fei Dong, None; Wei Li, None; Zuguo Liu, None
  • Footnotes
    Support  National Natural Science Foundation of China NSFC, No.81100639
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 6007. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      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.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose: : To explore the role of Notch signaling in corneal endothelial-mesenchymal transformation (EnMT).

Methods: : 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.

Results: : 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.

Conclusions: : It was indentified for the first time that Notch signaling is a novel therapeutic target for corneal endothelial fibrogenic disorders.

Keywords: cornea: endothelium • EMT (epithelial mesenchymal transition) • enzymes/enzyme inhibitors 
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×