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Updated: Jul 5, 2026
Determining the Toxicity of UV Radiation and Chemicals on Primary and Immortalized Human Corneal Epithelial Cells
Published on: July 22, 2021
Modulation of matrix metalloproteinases by ultraviolet radiation in the canine cornea
Heather L Chandler1, Donna F Kusewitt, Carmen M H Colitz
1Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, 1900 Coffey Road, Columbus, OH 43201, USA. chandler.111@osu.edu
Purpose:
To determine whether ultraviolet (UV) radiation can modulate expression and regulation of matrix metalloproteinases (MMP) in the canine cornea and to examine the expression of MMPs in canine chronic superficial keratitis (CSK).
Methods:
Immunohistochemistry for MMP-2 and MMP-9 was performed on samples of CSK. In vitro, canine corneal epithelial cell (CEC) and stromal cell cultures were exposed to UV-irradiation. Following 2, 8 or 24 h, cells were harvested. MMP expression was examined by zymography, and RT-PCR was used to examine expression of Slug and Snail. CEC cultures treated with an EGFR inhibitor or a p38 inhibitor were UV-exposed and harvested 24 h later to examine expression of MMPs, Slug and Snail.
Results:
Canine CSK had increased immunopositivity for both MMP-2 and MMP-9 compared to normal canine corneas. In vitro, CEC and stromal cell cultures exposed to UV showed generally increased expression of MMP-2, -9, Slug, and Snail; this response was dose and time dependent. Inhibition of the EGFR pathway did not prevent increased expression of MMP-2, -9, Slug or Snail in UV-exposed CEC; however, p38 inhibition did attenuate UV induction.
Conclusions:
We have found increased expression of MMPs in clinical samples of CSK compared to normal corneas. In addition, we have shown that there is a temporal association and dose dependency between UV exposure and production of MMPs, Slug, and Snail. These findings suggest that overexpression of MMPs due to UV-exposure may be linked to changes in the cornea that allow an influx of inflammatory cells and vascularization.
Insights
Ultraviolet radiation increases matrix metalloproteinases (MMPs) and associated proteins in canine corneas, potentially contributing to inflammation and vascularization in chronic superficial keratitis (CSK). This UV-induced MMP expression is dose- and time-dependent.
Area of Science:
- Ophthalmology
- Veterinary Medicine
- Cell Biology
Background:
- Matrix metalloproteinases (MMPs) play a role in corneal remodeling.
- Chronic superficial keratitis (CSK) is an inflammatory condition of the canine cornea.
- Ultraviolet (UV) radiation is a potential environmental factor influencing corneal health.
Purpose of the Study:
- To investigate the effect of UV radiation on MMP expression in canine corneas.
- To examine MMP expression in canine CSK.
- To elucidate the regulatory pathways involved in UV-induced MMP production.
Main Methods:
- Immunohistochemistry was used to assess MMP-2 and MMP-9 in CSK samples.
- Canine corneal cells (epithelial and stromal) were exposed to UV radiation in vitro.
- Gene expression of MMPs, Slug, and Snail was analyzed using zymography and RT-PCR.
- The role of EGFR and p38 signaling pathways was investigated using specific inhibitors.
Main Results:
- Canine CSK samples showed elevated levels of MMP-2 and MMP-9 compared to normal corneas.
- UV exposure in vitro led to increased expression of MMP-2, MMP-9, Slug, and Snail in a dose- and time-dependent manner.
- p38 pathway inhibition attenuated UV-induced MMP expression, while EGFR inhibition did not.
Conclusions:
- Increased MMP expression is observed in canine CSK.
- UV radiation is directly linked to increased MMP, Slug, and Snail production in canine corneal cells.
- UV-induced MMP overexpression may contribute to corneal inflammation and vascularization in CSK.
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