Increased Expression of Tenascin-C-binding Epithelial Integrins in Human Bullous Keratopathy Corneas

Abstract

We previously found an abnormal deposition of an extracellular matrix glycoprotein, tenascin-C (TN-C), in human corneas with pseudophakic/aphakic bullous keratopathy (PBK/ABK). In this work, we studied cellular TN-C receptors in normal and PBK/ABK corneas. Cryostat sections of normal and PBK/ABK corneas were stained by immunofluorescence for TN-C receptors: α2, α8, α9, αVβ3, β1, and β6 integrins, and annexin II. β6 integrin mRNA levels were assessed by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) using β2-microglobulin gene to normalize the samples. In PBK/ABK compared to normal corneas, relatively minor changes were observed for α2 and β1 integrins, and for annexin II. α8, α9, and β6 subunits of TN-C receptors, α8β1 α9β1, and αVβ6, respectively, were absent from normal central corneas but were found in the central epithelium of PBK/ABK corneas. β6 integrin showed the most significant accumulation. It correlated best with the expression of TN-C rather than with the expression of other αVβ6 ligands, fibronectin, and vitronectin. RT-PCR analysis also showed elevated levels of β6 mRNA in PBK/ABK compared to normal corneas. Therefore, accumulation of TN-C in PBK/ABK corneas was accompanied by an increased expression of its three binding integrins, especially αVβ6 in the corneal epithelium. The interaction of tenascin-C with these integrins may contribute to the fibrotic process that occurs in PBK/ABK corneas.