Hypoxia Affects Cell Migration and Wound Healing by Altering Basal Lamina Proteins and Focal Adhesion Turnover

Abstract

Corneal disease and injury remain a major cause of blindness according to the World Health Organization. Certain conditions such as diabetes, corneal infection, and corneal ulceration may cause the cornea to be exposed to a hypoxic state for extended periods of time. Over 95% of the new cases of diabetes are Type II. In these patients, a simple wound can lead to complications which are compounded by the reduced ability to recover from hypoxic stress. An ex vivo corneal organ culture model was employed to examine cell migration. After a 24 hour exposure to hypoxia healing is delayed by 6 hours compared to control. In addition, there is a morphological change at the leading edge of cells. We hypothesize that hypoxia affects cell migration and wound healing by altering the regulation of basal lamina proteins and the turnover of focal adhesions. We determined that wounded rat corneas exposed to a hypoxic environment display decreased epithelial expression of syndecan‐1 and fibronectin. The localization of fibronectin throughout the epithelium and stroma is altered in the hypoxic cornea. Additional studies examined the alterations in expression and co‐localization of focal adhesion proteins. Hypoxia caused a change in the localization of vinculin and paxillin along the basal lamina and within the epithelium. Furthermore, there was a change in localization along the basal lamina of Y118 paxillin in the hypoxic cornea. By determining the changes in basal lamina composition and characterizing the changes in regulation and dynamics of focal adhesion proteins, we aim to improve the treatment of delayed wound healing associated with corneal hypoxia.