Epithelial-mesenchymal transition (EMT) occurs as part of development, tissue repair, and tumor progression. Complete EMT is characterized by transformation of closely associated immobile epithelial cells into individual motile fibroblast-like cells. This phenotypic change is characterized by disruption of all cell-cell junctions and increased protease production. EMT is stimulated by growth factors, and in all cases thus far studied, EMT appears to be controlled by transcription factors belonging to the Snail family.
We demonstrate that Slug is required for corneal epithelial cell migration from murine corneal explants in vitro, and confirm the importance of Slug during EMT in the cornea by demonstrating the strong association between Slug expression and successful corneal wound healing in canine eyes in vivo. Slug is transiently expressed at the margins of healing corneal wounds and decreased Slug expression at corneal wound margins is accompanied by failure of EMT in non-healing corneal erosions of dogs. Finally, enhanced expression of Slug in corneal explants due to adenoviral transfection or tetracycline treatment increases the rate of epithelial cell migration.
UVR exposure of the cornea leads to increased expression of markers of EMT, including Snail and Slug and MMPs. Canine chronic superficial keratitis (CSK) is an inflammatory disease associated with UVR exposure. Our findings suggest that overexpression of MMPs due to UVR exposure may be linked to changes in the cornea during CSK that allow an influx of inflammatory cells and neovascularization.
We also demonstrate that EMT occurs in lens epithelial cells (LEC) during the repopulation of the lens capsule following cataract surgery with the subsequent development of posterior capsular opacification (PCO). In addition, there is increased expression of cyclooxygenase-2 (COX-2) in clinical samples of canine cataracts and PCO. Inhibiting the enzymatic activity of COX-2 effectively prevented EMT of LEC in our ex vivo model of PCO.
The findings reported here demonstrate that partial EMT occurs in a variety of situations in differentiated epithelial cells of the adult anterior eye. Understanding the molecular events that initiate partial EMT in CEC and LEC will provide important insights into the pathology of ocular diseases and ways to control the process.