Expression of keratin 12 and maturation of corneal epithelium during development and postnatal growth

PURPOSE. To determine the kinetics of corneal epithelial maturation during embryonic development and postnatal growth. METHODS. Expression patterns of keratin (K)12 and K14 were determined in mouse embryos (embryonic days [E] 15.5 - 19.5), corneas of postnatal day (P) 0 to 10 months, and healing corneas after epithelial debridement in P30 and P90 mice. The expression of alkaline phosphatase (AP) was determined during postnatal growth and healing of epithelial debridement of Krt12(Cre/Cre)/ZAP bitransgenic mice. RESULTS. During embryonic development, K12 expression by corneal peridermal epithelium commenced at E15.5. In the period from E15.5 to P10, the expression of K12 was restricted to the suprabasal and/or superficial cells of the corneal epithelium, whereas the K14 expression was restricted to the basal cells. After P30, K12 expression was sporadically detected in the basal corneal epithelium, and the number of K12-positive basal cells increased as the mice grew older. The number of K14-positive cells that coexpressed K12 increased with age and reached a plateau after P180. Healing of the debrided epithelium facilitated the increase in K14-positive cells that coexpressed K12. Many basal cells of Krt(12Cre/Cre)/ZAP mice remained undifferentiated and expressed LacZ at P15, and they then differentiated to express Cre, which leads to excision of LacZ and AP expression. CONCLUSIONS. In the mouse, the corneal epithelium does not become fully mature until 3 to 6 months after birth, in that a significant number of corneal basal epithelial cells of young mice (< P30), which derive from embryonic surface ectoderm remain undifferentiated and serve as corneal epithelial progenitor cells. These progenitor cells may have some stem cell characteristics.