Vitronectin: a migration and wound healing factor for human corneal epithelial cells

PURPOSE: The stratified squamous epithelial covering of the cornea provides one of the first physical and immunological lines of defense. A breach in its integrity results in a wound healing response that resolves quickly. However, under certain conditions-for example, when migrating cells are unable to adhere to the basement membrane-healing may be delayed. The aim of this study was to determine whether vitronectin (VN) promotes corneal epithelial wound healing.

METHODS: Primary human corneolimbal epithelial cells and the human corneal epithelial cell (HCEC) line were cultured and monitored to determine the rate of epithelial recovery after injury. Human corneas were placed in organ culture and the epithelium debrided. Therapeutic contact lenses (CLs) soaked in saline or coated in a solution of recombinant human VN were applied and the epithelium assessed histologically after 7 days.

RESULTS: Vitronectin (5 μg/mL) significantly enhanced the wound closure rate in cultured HCECs as well as in primary human corneal epithelial cells. Wound recovery was significantly blocked with a cyclic arginine-glycine-aspartate (RGD) peptide (10 μg/mL), a neutralizing antibody to VN (25 μg/mL) as well as after transiently silencing β5-integrin. Wound closure was not related to the effect of VN on cell proliferation. Finally, incubating epithelial-debrided human corneas with CLs loaded in VN resulted in effective re-epithelialization of the injured surface.

CONCLUSIONS: Vitronectin is a key extracellular matrix protein that expedites corneal epithelial wound recovery in vitro and ex vivo. Delivery of VN on therapeutic CLs may be an effective and efficient way to treat patients with persistent epithelial defects of the ocular surface.