Peripheral (not central) corneal epithelia contribute to the closure of an annular debridement injury

Abstract

Corneal epithelia have limited self-renewal and therefore reparative capacity. They are continuously replaced by transient amplifying cells which spawn from stem cells and migrate from the periphery. Because this view has recently been challenged, our goal was to resolve the conflict by giving mice annular injuries in different locations within the corneolimbal epithelium, then spatiotemporally fate-mapping cell behavior during healing. Under these conditions, elevated proliferation was observed in the periphery but not the center, and wounds predominantly resolved by centripetally migrating limbal epithelia. After wound closure, the central corneal epithelium was completely replaced by K14+ limbal-derived clones, an observation supported by high-resolution fluorescence imaging of genetically marked cells in organ-cultured corneas and via computational modeling. These results solidify the essential role of K14+ limbal epithelial stem cells for wound healing and refute the notion that stem cells exist within the central cornea and that their progeny have the capacity to migrate centrifugally.