Article Text

Download PDFPDF

TGF-β and transglutaminase 2 work together to cause cataracts

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

A molecular study has shown for the first time that transglutaminase 2 (TGase 2) overexpression induced by transforming growth factor β (TGF-β) is a key step in the development of some cataracts.

The investigators showed TGase 2 mRNA and TGase 2 protein in human lens epithelial cells taken from anterior polar cataracts but not in cells from nuclear cataracts or healthy lens cells.

When they added TGF-β to cultures of human lens epithelial cells (HLE B-3) TGase 2 expression increased in a time and dose dependent way, compared with untreated cell cultures.

The investigators then treated cultures unprimed or primed by TGF-β with fluorescein cadaverine to see whether fibronectin cross linking seen in cataracts was due to increased TGase 2 activity. Fluorescent foci on the surface of the primed cells confirmed that it was. Separate staining with antibody to fibronectin showed abundant fibrils on the surface of primed cells but hardly any on unprimed cells. Superimposed images obtained with each label showed coincident surface labelling of the primed cells, indicating that TGF-β induces Tgase 2 cross linking of fibronectin. Finally, double staining with fluorescein cadaverine and fibronectin antibody showed greater, co-localised staining of HLE B-3 cells transfected with TGase 2 gene compared with control cultures transfected with vector only.

TGase 2 activity has been suspected in cataract formation as it can cross link extracellular matrix proteins with very stable isopeptide bonds. TGF-β is another key factor in cataract formation, but exactly how it interacts with TGase 2 was not known.