αVβ6 Integrin Promotes Corneal Wound Healing

PURPOSE. To appreciate the role of the integrin alpha v beta 6 in corneal wound repair, corneal debridement and keratectomy in beta 6 knockout (beta 6(-/-)) mice were examined. METHODS. Either a 2-mm debridement or keratectomy was made in 129SVE wild type mice (WT) and beta 6(-/-) mice and allowed to heal for up to 4 months. The pattern of corneal restoration was studied "in vivo" by slit lamp and in tissue sections by means of both light and electron microscopy. In addition, alpha v beta 6, alpha 6 beta 4, laminin, and fibronectin were evaluated by indirect immunofluorescence microscopy and/or Western blot analysis. RESULTS. alpha v beta 6 expression was upregulated in migrating corneal epithelium after a keratectomy. Healing rates were unaffected in debridement wounds, but were significantly slowed in keratectomy wounds. Most dramatically, mice lacking alpha v beta 6 had a severe defect in basement membrane zone (BMZ) regeneration. Levels of laminin were greatly reduced and no BMZ reformation was observed in transmission electron microscopy (TEM). In addition, hemidesmosome reformation was also impaired in the beta 6(-/-) mice. Analysis of the hemidesmosome component alpha 6 beta 4 indicated that normal amounts of this integrin were synthesized, suggesting that the defect was in reassembly of the hemidesmosomes. Finally, fibronectin persisted in the BMZ for as long as 4 months after keratectomy in the beta 6(-/-) mice. CONCLUSIONS. It is hypothesized that the lack of alpha v beta 6 leads to reduced laminin production during wound repair. This lack of laminin prevents reassembly of the BMZ and mature hemidesmosomes after keratectomy in beta 6(-/-) mice. (Invest Ophthalmol Vis Sci. 2011;52:8505-8513) DOI:10.1167/iovs.11-8194