What is it about?

Purpose Transglutaminase (TG)-2 is a widespread multi-functional protein produced in all live cells. The aim of the current study was to explore the role of TG-2 in corneal barrier function and its possible control of epithelium junctional proteins and transcription factors. Methods Corneal barrier function to ions in TG-2−/− and TG-2+/+ mice was measured by Ussing chamber test. Hypo-osmolar water or FITC-dextran was placed on top of mouse eyes to test the corneal barrier function to water and proteins. Western blots, qPCR and immunofluorescent staining were used to examine the expression of tight junction proteins in TG-2−/− and TG-2+/+ mouse corneas, and also in TG-2 knockdown human corneal epithelial cells. Results Corneal explants from TG-2−/− mice had a lower trans-epithelial electrical resistance compared to TG-2+/+ mice. When challenged by hypo-osmolar water, the central corneal thickness of TG-2−/− mice rose faster, and these mice had a faster rise of light in the anterior chamber after eye exposure to FITC-dextran, compared to TG-2+/+. Claudin-1 protein and transcript levels were decreased in the cornea of TG-2−/− mice and in TG-2 knockdown human corneal epithelial cells. Slug which earlier reported reducing Claudin-1 transcription, was raised at both protein and transcript level in TG-2 knockdown cells. TG-2 and Claudin-1 protein levels were unaffected in shRNA and shTG cells after MG132 treatment, while Slug accumulated in treated cells. Conclusion TG-2 may positively control Claudin-1 through suppressing Slug at gene level, and thus it is important for proper eye barrier function.

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Why is it important?

There are no easy way to treat diseases of the eye surface

Perspectives

Molecular intervention may be important for future therapies of conditions like dry eye and allergies.

Prof Louis Tong
National University of Singapore

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This page is a summary of: Transglutaminase-2 is critical for corneal epithelial barrier function via positive regulation of Claudin-1, The Ocular Surface, April 2023, Elsevier,
DOI: 10.1016/j.jtos.2023.04.002.
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