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I.M. Wolff, A.S. Menko; Migration of Lens Epithelial Cells on the Posterior Lens Capsule Is Blocked By Inhibition of Src Family Kinases . Invest. Ophthalmol. Vis. Sci. 2005;46(13):2868.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To examine whether blocking the activation of Src kinases would prevent the proliferation and migration of lens epithelial cells along the posterior lens capsule, in a model for posterior capsule opacification (PCO). Methods: Chick embryo lens capsule cultures were prepared according to a procedure described by Liu et al. (IOVS 37:906). The lens capsules, with lens epithelial cells still attached in the equatorial zone, were pinned to a culture dish and incubated in Media 199, both with and without 10% fetal calf serum. Movement of the lens epithelial cells to the posterior aspects of the capsule was followed by phase contrast microscopy. Immunolocalization was performed with antibodies to ß–catenin and activated Src. Expression of PCNA and activation of focal adhesion kinase (FAK) were determined by immunoblotting. In cultures, Src kinases were inhibited with PP1. Results: PCO can occur from a few months to a few years after cataract surgery, as lens epithelial cells that remained associated with the lens capsule proliferate and migrate to the posterior capsule. This causes wrinkling and clouding of the posterior capsule, blocking vision. In our model, lens epithelial cells cultured on their capsule in the absence of serum displayed only limited migration towards the posterior capsule. Exposure to fetal calf serum signaled these epithelial cells to proliferate, migrate, and completely cover the posterior capsule within 6 days. FAK, a molecular marker of cell migration, was activated in our PCO culture model. Distinct morphological changes, characteristic of an epithelial to mesenchymal transition, occurred as the cells traversed the posterior capsule. However, the migrating cells still maintained cadherin junctions as was evidenced by localization of beta–catenin to the cell–cell borders. We investigated the role of Src kinases in PCO. In the migratory cells high levels of active Src kinases were recruited to cell–cell borders. PP1 inhibition of Src kinase activity suppressed proliferation and the activation of FAK as well as blocked the movement of the cells onto the posterior capsule. Conclusions: Following sham cataract surgery, exposure of the inside of the lens capsule to serum growth factors signals the remaining lens epithelial cells to migrate. The epithelial to mesenchymal transition of these lens, their proliferation and their migration along the posterior capsule is dependent on the activation of Src kinases.
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