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The Replacement Hypothesis: Corneal Stem Cell Origin Epithelia Are Replaced by Limbal Stem Cell Origin Epithelia in Mouse Cornea During Maturation

Hayashi, Yasuhito MD, PhD*,†; Watanabe, Narumi MS*; Ohashi, Yuichi MD, PhD*

doi: 10.1097/ICO.0b013e318269c83f
Article

Purpose: Previous studies have shown that the stem cells of corneal epithelia are located at the limbal basal layer. Limbal stem cells are believed to be the source of corneal epithelial cell proliferation and differentiation. This study tested the replacement hypothesis, which suggests that corneal stem cell origin epithelia may be replaced by limbal stem cell origin epithelia after 2 weeks of age in mice.

Methods: The cytokeratin 12 expression pattern in the cornea was examined using K12 IRES-Cre and Cre reporter mice.

Results: Before 2 weeks of age, K12IRES-Cre expression in corneal epithelia showed a mosaic pattern. After 2 weeks of age, centripetal K12IRES-Cre expression gradually elongated from the limbal area. Around 12 weeks of age, the mosaic expression pattern disappeared from the center of the cornea. Temporal and spatial observations of K12IRES-Cre expression patterns suggested that the mosaic pattern cells proliferated and amassed at the same position from day 15.5 of the embryonic stage at the latest.

Conclusions: Therefore, these cells were considered corneal stem cell origin epithelia. In contrast, centripetal pattern cell populations were considered limbal stem cell origin epithelia because they originated from the limbal area and moved to the center of the cornea. These observations suggest that corneal stem cell origin epithelia are replaced by limbal stem cell origin epithelia after 2 weeks of age in mice.

Departments of*Ophthalmology

Regenerative Medicine, Ehime University School of Medicine, Ehime, Japan.

Reprints: Yasuhito Hayashi, Department of Ophthalmology, Ehime University School of Medicine, 454 Shitsukawa, Toon, Ehime 791-0295, Japan (e-mail: yhayashi@m.ehime-u.ac.jp).

Supported by the Ministry of Education, Culture, Sports, Science and Technology of Japan (C23592608).

The authors have no conflicts of interest to declare.

© 2012 Lippincott Williams & Wilkins, Inc.