Corneal epithelial repair: Role of AP-2 transcription factor

Purpose. We have recently shown that AP-2 participates in regulating the expression of gelatinase B, a degradative enzyme expressed during corneal wound healing. AP-2 has also been shown to regulate expression of other epithelial genes in cell culture. In this study, we further examine the role of AP-2 in maintenance and repair of the corneal epithelium. Methods. AP-2 protein was immunolocalized on sections of normal rat cornea and healing partial keratectomy wounds. In cell culture, we overexpressed wild-type AP-2 in the rabbit corneal cell line SIRC. Results. We have specifically localized AP-2 to the basal epithelial cells of the cornea and this localization appears significantly upregulated in cells migrating to heal a wound. In contrast, AP-2 expression is decreased in epithelium migrating to heal a thermal wound in which there is poor adhesion between the epithelium and the stroma. The colonies, of SIRC cells stably transformed with wild-type AP-2 exhibit drastically altered epithelial cell behavior, including the appearance of large clusters of cells reminiscent of stratification and cornification. Adhesion assay studies also revealed that a number of the colonies of stably transformed cells are altered in their ability to adhere to various matrices including vitronectin and collagen type I. Interestingly, the severity of cell phenotype in the transformed SIRC clones correlates well with the level of AP-2 mRNA expressed as determined by northern blot analysis. Assessments of other epithelial behaviors of the SIRC clones, including their migration ability, will also be presented. Conclusions. Together these results suggest that AP-2 plays an essential role in controlling adhesion between the corneal epithelium and the corneal stroma.