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Related Experiment Video

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An Ex Vivo Model to Study Early Changes in Keratoconus.

Pritpal Kaur1, Loren Moon1, Deepti Sharma1

  • 1Wilmer Eye Institute, Johns Hopkins Medical Institute, Baltimore, MD; and.

Cornea
|June 3, 2025
PubMed
Summary

This study developed an ex vivo model simulating eye rubbing to understand keratoconus (KC) progression. The model successfully replicated key KC features, including Bowman layer breaks and epithelial changes, offering a tool for developing new KC therapies.

Keywords:
corneal biomechanicscorneal epitheliumex vivo modelkeratoconus

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Area of Science:

  • Ophthalmology
  • Biomechanical Engineering
  • Cell Biology

Background:

  • Eye rubbing is a significant risk factor for keratoconus (KC) development and progression.
  • Current research lacks adequate ex vivo models to simulate the mechanical stresses of eye rubbing in KC.

Purpose of the Study:

  • To develop and validate an ex vivo model that simulates eye rubbing to study early keratoconus.
  • To analyze the biomechanical and molecular changes in corneal tissues subjected to simulated eye rubbing.

Main Methods:

  • Human corneal stromal caps and mouse eyes were subjected to cyclical mechanical strain (3% strain) to mimic eye rubbing.
  • Hematoxylin and eosin staining and F-actin immunostaining were used to evaluate structural changes in the Bowman layer and corneal epithelium.
  • Wnt10a and Col12a1 mRNA levels were quantified in stretched and unstretched corneal epithelium.

Main Results:

  • Mechanical strain significantly increased Bowman layer breaks in human corneas (P = 0.003).
  • Mouse corneal epithelium showed increased basal cell width (15%, P < 0.001) and reduced apical cell height (8%, P = 0.025) under strain.
  • Wnt10a and Col12a1 mRNA levels decreased by approximately 67% and 65% respectively in strained mouse epithelium (P = 0.0312).

Conclusions:

  • The developed ex vivo model effectively simulates key pathological changes observed in early keratoconus.
  • This model recapitulates Bowman layer defects, epithelial cell alterations, and specific gene expression changes associated with KC.
  • The model serves as a valuable platform for investigating keratoconus pathogenesis and developing targeted therapeutic interventions.