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Updated: Jan 23, 2026

In Vitro and In Vivo Models to Study Corneal Endothelial-mesenchymal Transition
Published on: August 20, 2016
ZEB1 insufficiency causes corneal endothelial cell state transition and altered cellular processing
Ricardo F Frausto1, Doug D Chung1, Payton M Boere1
1The Stein Eye Institute, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America.
The zinc finger e-box binding homeobox 1 (ZEB1) gene is crucial for cell state changes. Its insufficiency causes posterior polymorphous corneal dystrophy (PPCD) via an endothelial to epithelial transition (EnET).
Area of Science:
- Cell Biology
- Developmental Biology
- Ophthalmology
Background:
- The zinc finger e-box binding homeobox 1 (ZEB1) transcription factor regulates epithelial to mesenchymal transition (EMT) and mesenchymal to epithelial transition (MET).
- ZEB1 is vital for cell lineage specification, wound healing, and disease processes.
- Posterior polymorphous corneal dystrophy (PPCD) is linked to ZEB1 insufficiency, offering a novel context to study EMT/MET.
Purpose of the Study:
- To investigate the role of ZEB1 in PPCD.
- To determine if corneal endothelial cells (CEnCs) undergo a MET-like transition in PPCD.
- To establish an endothelial to epithelial transition (EnET) as a corollary to the EMT/MET paradigm.
Main Methods:
- Generated a cell-based model of PPCD using CRISPR-Cas9 to knock out ZEB1 in CEnCs.
- Performed transcriptomic analyses to compare ZEB1-deficient CEnCs with controls.
- Conducted functional studies to assess cellular phenotype changes.
Main Results:
- ZEB1 knockout in CEnCs induced a cadherin-switch and an epithelial-like transcriptomic and cellular phenotype.
- These changes are consistent with a MET-like process, termed endothelial to epithelial transition (EnET).
- The findings support the hypothesis that CEnCs undergo EnET in PPCD.
Conclusions:
- EnET in PPCD is a MET-like process driven by ZEB1 insufficiency.
- EnET serves as a corollary to the established EMT/MET paradigm.
- This study provides new insights into ZEB1-mediated cell state transitions in corneal endothelial cells.
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