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N. Terai, K. Terai, Y. Hayashi, T.–I. Chikama, W.W. Kao; Differentiation and Maturation of Corneal Epithelium During Embryonic Development and Postnatal Growth . Invest. Ophthalmol. Vis. Sci. 2005;46(13):4771.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To determine the kinetics of corneal epithelium differentiation and maturation during embryonic development and postnatal growth. Methods: Expression patterns of keratin 12 (K12) and k14 was determined by immunofluorescence staining of paraffin sections and epithelial cell suspension from mouse embryos (E15.5–19.5) and postnatal day P15 to 10 months, and healing corneas of epithelium debridement at P90. The expression pattern of reporter alkaline phosphatase (AP) activity during postnatal growth of Krt12Cre/Cre/ZAP bitransgenic mice was used to determine epithelial cell differentiation and maturation postnatal. Results: During embryonic development, K12 expression commences at E15 and peaks at E17.5, decline to a low level at birth, and then increases from P4 and reaches a plateau at 3 weeks and thereafter. In the period E15.5–P21, the expression of K12 was mostly detected in the suprabasal cells of corneal epithelium, while the K14 expression was found in the basal cells. After P21, K12 expression could be readily detected, albeit sporadic in the basal corneal epithelium, and the number of K12–positive basal cells increased as the mice grew older. Double immune staining of epithelial cell suspension with anti–K12 and K14 antibodies indicated that the number of K14 positive cells simultaneously expressing K12 increased with ages of the experimental mice, 27.1 ± 15.5 % in P15, 31.3 ± 11.5 % in P21, 31.7 ± 11.5 % in P30, 34.8 ± 8.8 % in P60, and 50.1 ± 7.3 % in P90, 69 ± 3.7% in P180, 69.1 ± 1.4 % in 10 month. At P90 stage, epithelial cell suspension from cornea of epithelial debridement revealed that K12 positive cells within K14 positive population were 55.1± 10.3 % in 24h, 56.3 ± 7.6 % in 48h, 59.8 ± 7.1 % in 72h, 68.5 ± 7.5 % in 4day, 70.8 ± 7.2 % in 5day, 70.8 ± 10,2 % in 7day, while naïve corneas maintained at about 50%. K12Cre/CreZAPtg/w mice that basal cells remained AP negative at P14 and positive at 3 months.Conclusions:In young mice (<P21), many basal corneal epithelial cells derived from embryonic surface ectoderm may maintain un–differentiated. The mouse corneal epithelium does not become fully mature until 3 months postnatal.
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