Increased expression of tenascin-C-binding epithelial integrins in human bullous keratopathy corneas

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: alpha (2), alpha (8), alpha (9), alpha (V)beta (3), beta (1), and beta (6) integrins, and annexin II. beta (6) integrin mRNA levels were assessed by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) using beta (2)-microglobulin gene to normalize the samples. In PBK/ABK compared to normal corneas, relatively minor changes were observed for alpha (2) and beta (1) integrins, and for annexin II. alpha (8), alpha (9), and beta (6) subunits of TN-C receptors, alpha (8)beta (1), alpha (9)beta (1), and alpha (V)beta (6), respectively, were absent from normal central corneas but were found in the central epithelium of PBK/ABK corneas. beta (6) integrin showed the most significant accumulation. It correlated best with the expression of TN-C rather than with the expression of other alpha (V)beta (6) ligands, fibronectin, and vitronectin. RT-PCR analysis also showed elevated levels Of beta (6) 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 alpha (V)beta (6) in the corneal epithelium. The interaction of tenascin-C with these integrins may contribute to the fibrotic process that occurs in PBK/ABK corneas.