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A novel transgenic mouse model for corneal scar visualization.

Irona Khandaker1, James L Funderburgh1, Moira L Geary1

  • 1Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, United States.

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A new transgenic mouse model allows researchers to visualize corneal fibrosis in real-time. This tool aids in studying scar development and testing new treatments for corneal opacities, offering hope beyond transplantation.

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Area of Science:

  • Ophthalmology
  • Regenerative Medicine
  • Genetics

Background:

  • Corneal opacities cause vision loss globally, often requiring transplantation.
  • Current mouse models lack visibility for studying corneal scarring.
  • Developing non-surgical treatments for corneal fibrosis is a key research area.

Purpose of the Study:

  • To develop and validate a transgenic mouse model for visualizing corneal fibrosis in vivo.
  • To assess the utility of this model in monitoring scar progression and treatment response.

Main Methods:

  • Utilized a Tg(Col3a1-EGFP)DJ124Gsat transgenic mouse line where EGFP expression marks collagen 3a1 (COL3a1) promoter activity.
  • Induced corneal scarring via alkali burn and mechanical ablation.
  • Analyzed opacities using stereomicroscopy and Spectral Domain optical coherent tomography.
  • Quantified fibrosis markers and scar volume using flow cytometry and ELISA.
  • Evaluated treatment effects using human corneal stromal stem cells and their exosomes.

Main Results:

  • The transgenic model successfully recapitulated corneal opacities and fibrosis post-injury.
  • EGFP expression correlated with COL3a1 upregulation and other fibrosis gene markers.
  • Increased EGFP signal intensity corresponded to scar volume and corneal thickening.
  • Treatment with stem cells/exosomes reduced EGFP expression, scar volume, and fibrosis markers.

Conclusions:

  • The Tg(Col3a1-EGFP)DJ124Gsat mouse line is a valuable tool for in vivo detection and monitoring of corneal fibrosis.
  • This model can facilitate the development and evaluation of novel therapies for corneal scarring.