IOVS Journal of Pharmacology and Experimental Therapeutics
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(Investigative Ophthalmology and Visual Science. 2007;48:1511-1517.)
© 2007 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.06-1060
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ß-Catenin Activation and Epithelial-Mesenchymal Transition in the Pathogenesis of Pterygium

Naoko Kato,1,2 Shigeto Shimmura,1,2 Tetsuya Kawakita,2 Hideyuki Miyashita,1 Yoko Ogawa,1 Satoru Yoshida,1,2 Kazunari Higa,1,2 Hideyuki Okano,3 and Kazuo Tsubota1,2

1From the Department of Ophthalmology; Keio University School of Medicine, Tokyo, Japan; the 2Department of Ophthalmology; Tokyo Dental College, Chiba, Japan; and the 3Department of Physiology; School of Medicine, Keio University, Tokyo, Japan.

PURPOSE. To investigate whether ß-catenin activation and epithelial-mesenchymal transition (EMT) is involved in the pathogenesis of pterygium.

METHODS. ß-Catenin and E-cadherin expression were examined in surgically excised tissue and eye bank corneas with intact pterygium. Snail and Slug, the transcriptional repressors of E-cadherin, and matrix metalloproteinase (MMP)-7, a down-stream gene regulated by ß-catenin were also investigated. Epithelial cells undergoing EMT-like changes were identified by double immunostaining for {alpha}-smooth muscle actin (SMA)/vimentin and cytokeratin 14. Transmission electron microscopy was used to examine the ultrastructure of the pterygial head.

RESULTS. Histopathology showed aberrant fibrotic proliferation beneath the pterygium epithelium, with epithelial processes extending into the stroma. Transmission electron microscopy revealed the dissociation of epithelial cells, which were surrounded by activated fibroblast-like cells. Characteristic downregulation of E-cadherin and intranuclear accumulation of ß-catenin and lymphoid-enhancer-factor-1 in pterygial epithelium were also observed by immunohistochemistry. Of note, epithelial cells extending into the stroma were positive for both {alpha}-SMA/vimentin and cytokeratin 14. Snail and Slug were immunopositive in the nuclei of pterygial epithelial cells, but not in normal corneal epithelial cells.

CONCLUSIONS. EMT of basal epithelial cells may play a key role in the pathogenesis of pterygium.






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