Visualizing the Contribution of Keratin-14+ Limbal Epithelial Precursors in Corneal Wound Healing

Abstract

Summary: It is thought that corneal epithelial injuries resolve by leading-edge cells “sliding” or “rolling” into the wound bed. Here, we challenge this notion and show by real-time imaging that corneal wounds initially heal by “basal cell migration.” The K14CreERT2-Confetti multi-colored reporter mouse was employed to spatially and temporally fate-map cellular behavior during corneal wound healing. Keratin-14+ basal epithelia are forced into the wound bed by increased population pressure gradient from the limbus to the wound edge. As the defect resolves, centripetally migrating epithelia decelerate and replication in the periphery is reduced. With time, keratin-14+-derived clones diminish in number concomitant with their expansion, indicative that clonal evolution aligns with neutral drifting. These findings have important implications for the involvement of stem cells in acute tissue regeneration, in key sensory tissues such as the cornea. : In this article, Di Girolamo and colleagues visualized the contribution of K14+ limbal epithelial precursors in resolving corneal epithelial debridement wounds. They noted that population pressure from the limbal perimeter is the main driver of K14+ basal cell displacement during the initial phase of injury repair. Keywords: cornea wound healing, limbal epithelial stem cells, K14CreERT2-Confetti transgenic mice, basal cell migration, organ-culture system, spatiotemporal image correlation spectroscopy, computational modeling