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R. J. Tsai, I. J. Wang, L. K. Yeh; De-Differentiation of Corneal Epithelial Cells After Basement Membrane Injury. Invest. Ophthalmol. Vis. Sci. 2009;50(13):1767.
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To understand the limbal stem cells differentiation, we hypothesize that limbal stroma support the niches environment for the differentiation of limbal stem cells. The change of corneal basal epithelial cells, losing of the characteristics of limbal stem cells, was due to the blockage of stromal niche environment by intact basement membrane.
We evaluated 10 recipient corneas which were taken from the patients who had received PKps. Those patients included 7 cases with keratoconus, 1 case suffered cornea ectasia due to previous LASIK surgery and 2 cases with corneal scarring and irregular astigmatism due to previous RK refractive surgery. Immunohistologic studies with K3, p63, CX43, ABCG2, FGF7, PCNA, beta-Catenin, p38MAPK, and MAPKAPK2 were evaluated.
The most positive results of immunohistologic studies were p63, ABCG2 and CX43. In normal central cornea epithelium, there was negative staining for p63 and ABCG2, but positive for CX43. However, in normal limbal epithelium, stainings of p63 and ABCG2 were positive in the basal epithelial layers; however, CX43 was negative in the basal layer epithelium. In wounded cornea epithelium, p63, ABCG2 and CX43 were strongly positive over the basal layer epithelium. These results demonstrated that the wounded corneal epithelial cells changed their differentiation pathways, which p63 and ABCG2 became positive in wounded corneal epithelial cells. However, the wounded corneal epithelial cells still shared the same differentiation markers of normal central corneal epithelial cells, in which they were all positive for CX43. In order to further understand the underline mechanism, we found the wounded corneal basal epithelial cells expressed p38MAPK and MAPKAPK2
Corneal stem cells differentiation may be modulated by corneal wounding. The disrupted basement membrane may allow leakage of some cytokines from the corneal stroma and modulated the differentiation of corneal epithelial cells which resulted in de-differentiation and became the progenitor cells of corneal epithelial cells. This phenomenon may be through the p38MAPK and MAPKAPK2 signaling pathways.
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