Abstract
Purpose: :
Examine the signaling mechanisms involved in cell migration and epithelial to mesenchymal transformation (EMT) during the development of posterior capsule opacification (PCO).
Methods: :
Chick lens capsular bags prepared by sham cataract surgery were placed in culture. Cell movement across the posterior capsule was documented microscopically. EMT was determined by expression of α–smooth muscle actin (α–SMA) and fibronectin. Mechanisms of migration and EMT were examined by inhibiting Src, ERK and p38 kinases using PP1, UO126 and SB203580, respectively.
Results: :
PCO, the major complication of cataract surgery, results from migration of residual lens epithelial cells onto the posterior capsule, their EMT and the subsequent wrinkling of the posterior capsule. In our PCO cultures lens cells covered the posterior capsule within three days, but no EMT markers were detected. By six days in culture, α–SMA and fibronectin were highly expressed and the posterior capsule was wrinkled. α–SMA expressing cells, all with a fibroblastic morphology, emerged both in the region of origin of the epithelial cells and in cells along the posterior capsule. Src, ERK and p38 kinases were examined for their role in lens cell migration vs. EMT in PCO. Inhibition of Src kinases blocked lens cell migration and EMT. Inhibitors of ERK and p38 kinases had little effect on cell migration but efficiently blocked EMT.
Conclusions: :
In PCO the migration of lens epithelial cells onto the posterior capsule precedes EMT. Signaling pathways for migration require Src, not ERK or p38 activity; EMT requires the function of Src, ERK and p38 kinases.
Keywords: posterior capsular opacification (PCO) • signal transduction • signal transduction: pharmacology/physiology