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Updated: Jun 10, 2026
Ex Vivo Corneal Organ Culture Model for Wound Healing Studies
Published on: February 15, 2019
Corneal morphogenesis during development and diseases
1Department of Ophthalmology, College of Medicine, University of Cincinnati, Cincinnati, OH 45267-0838, USA. winston.kao@uc.edu
Objective:
To review the use of genetically modified mouse lines for elucidating corneal morphogenesis during embryonic development and diseases.
Methods:
Transgenesis and gene-targeting techniques were used to create doxycycline-inducible mouse models (tet-On) to express transgenes or ablation of LoxP-modified genes or both in corneal cells, e.g., epithelial cells, and keratocytes and periocular mesenchymal cells of neural crest origin.
Results:
Two driver mouse lines, i.e., Krt12-rtTA and Kera-rtTA, were created, which express reverse tetracycline transcription activator (rtTA) in corneal epithelial cells and keratocytes, respectively. Bitransgenic (Krt12-rtTA/tet-o-FGF7) and triple transgenic mice (Krt12rtTA/tet-o-Cre/Ctnnb1 and Kera-rtTA/tet-o-Cre/Ctnnb1) were obtained through cross-breeding tet-o-FGF7, tet-o-Cre, and Ctnnb1 mice. On doxycycline induction, overexpression of FGF7 by corneal epithelial cells of bitransgenic Krt12-rtTA/tet-o-FGF7 mice caused nuclear translocation of beta-catenin and epithelium hyperplasia resembling human ocular surface squamous neoplasia; in triple transgenic mice (Krt12rtTA/tet-o-Cre/Ctnnb1), constitutive nuclear translocation of mutant beta-catenin (loss of exon 3) leads to hyper proliferation of corneal epithelial cells; in comparison of expression of beta-catenin mutant protein by migrating, periocular mesenchymal cells of Kera-rtTA/tet-o-Cre/Ctnnb1 caused eyelid malformation.
Conclusions:
Use of genetically modified mice is of great value to study the pathophysiology of ocular surface defects resulting from genetic mutations.
Insights
Genetically modified mouse models reveal how genetic mutations cause corneal defects. These models, using doxycycline-inducible systems, allow precise control over gene expression to study developmental processes and diseases.
Area of Science:
- Ophthalmology
- Developmental Biology
- Genetics
Background:
- Corneal morphogenesis is a complex process crucial for vision.
- Understanding genetic mutations underlying corneal diseases is essential for developing effective treatments.
Purpose of the Study:
- To review the utility of genetically modified mouse lines in studying corneal development and disease.
- To highlight the application of doxycycline-inducible systems for precise genetic manipulation in corneal research.
Main Methods:
- Development of doxycycline-inducible (tet-On) mouse models using transgenesis and gene targeting.
- Creation of driver lines (Krt12-rtTA, Kera-rtTA) for specific gene expression in corneal cells.
- Generation of bitransgenic and triple transgenic mice to study gene function and ablation.
Main Results:
- Overexpression of FGF7 in corneal epithelial cells induced beta-catenin nuclear translocation and hyperplasia, mimicking ocular surface squamous neoplasia.
- Constitutive nuclear translocation of mutant beta-catenin in corneal epithelial cells led to hyperproliferation.
- Expression of mutant beta-catenin in periocular mesenchymal cells resulted in eyelid malformation.
Conclusions:
- Genetically modified mice are invaluable tools for investigating the pathophysiology of ocular surface defects.
- These models facilitate the study of genetic mutations impacting corneal development and disease progression.
