Inhibition of lens epithelial cell adhesion by the calcium antagonist Mibefradil correlates with impaired integrin distribution and organization of the cytoskeleton

Background: Posterior capsule opacification is the most common complication of primary cataract surgery and is caused by migration and proliferation o f residual lens epithelial cells onto the posterior capsule. Interfering wi th the mechanisms involved in cell adhesion is a suitable approach to preve nt posterior capsule opacification. Methods: Mibefradil, a T-type calcium-c hannel blocker, was used to examine the influence on adhesion-mediating mec hanisms in human lens epithelial cells derived from cataract surgery. Adhes ion was evaluated by light microscopy on the anteri- or capsules. Expressio n of integrin receptors was studied by flow cytometry. The influence on the distribution of integrin receptors on the cell surface and the organizatio n of the cytoskeleton was examined by immunofluorescence using a confocal m icroscope. Results: The calcium-channel blocker Mibefradil inhibited cell a dhesion on the anterior capsule wall at concentrations between 10 and 100 m uM. The cells expressed the integrin subunits beta1 and alpha3. Mibefradil distinctly impaired the distribution of these integrins on the cell surface in culture. The cells express the cytoskeletal components actin, vimentin and, very weakly, cytokeratin. The structural organization of the actin fil aments and vimentin was strongly disrupted with pronounced fragmentation of the actin filaments in the presence of the calcium-channel blocker. Conclu sion: The results suggest that the inhibition of cell adhesion by the calci um-channel blocker Mibefradil involves the impairment of integrin-mediated mechanisms. The use of this calcium antagonist appears to be a suitable the rapeutic approach to prevent posterior capsule opacification.