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In Vitro and In Vivo Models to Study Corneal Endothelial-mesenchymal Transition
Published on: August 20, 2016
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Cell derived matrices from bovine corneal endothelial cells as a model to study cellular dysfunction.
Iman Jalilian1, Santoshi Muppala2, Maryam Ali1
1Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA, 95616, USA.
Experimental Eye Research
|November 7, 2022
Summary
Transforming growth factor-β (TGF-β) alters corneal extracellular matrix stiffness, while ascorbic acid (AA) modulates oxidative stress pathways in Fuchs endothelial corneal dystrophy (FECD). These findings clarify the roles of soluble factors in FECD pathogenesis.
Area of Science:
- Ophthalmology
- Corneal Biology
- Extracellular Matrix Research
Background:
- Fuchs endothelial corneal dystrophy (FECD) is a progressive disease affecting corneal structure and cell survival.
- Oxidative stress and TGF-β pathways are implicated in FECD pathogenesis and endothelial cell loss.
- The impact of ascorbic acid (AA) and TGF-β on the corneal endothelial cell matrix composition and rigidity in FECD is not well understood.
Purpose of the Study:
- To investigate the effects of AA, TGF-β1, and TGF-β3 on the deposition, ultrastructure, stiffness, and composition of the extracellular matrix (ECM) secreted by primary bovine corneal endothelial cells (BCECs).
Main Methods:
- Primary bovine corneal endothelial cells (BCECs) were treated with AA, TGF-β1, and TGF-β3.
- ECM deposition and ultrastructure were analyzed using immunofluorescence and electron microscopy post-decellularization.
- Matrix stiffness was measured using Atomic Force Microscopy (AFM).
- Proteomics and Gene Ontology analysis were performed to identify modulated pathways and protein expression.
Main Results:
- TGF-β1 and TGF-β3 treatments led to significantly lower matrix modulus compared to controls.
- No significant difference in matrix stiffness was observed between AA-treated cells and controls.
- AA modulated oxidative stress pathways, while TGF-β induced expression of collagen IV, laminin, and lysyl oxidase homolog 1.
Conclusions:
- Soluble factors like TGF-β and AA differentially regulate the corneal endothelial cell matrix.
- These molecular pathways provide insights into the pathogenesis of FECD.
- Understanding these interactions is crucial for developing targeted therapies for corneal diseases.

