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Manuel P. Deprez, Michael J. Nicolas, Alexandre P. Moulin, Leonidas Zografos, Francois Majo; Expression Of The Stem Cell Markers ABCG2/BCRP, Bmi-1, P63alpha And C/EBPdelta In The Normal Human Cornea: An Immunohistochemical Study. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5115.
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Many studies have tried to characterize corneal epithelial stem cell markers based on their restricted expression in the basal cell layer of the limbal epithelium. This study focused on markers identified by a functional approach. ABCG2/BCRP, an ATP-transporter protein, identifies a population of human limbal epithelial cells with a high colony-forming efficiency in vitro. C/EBPΔ and Bmi-1 identify quiescent stem cells in the limbus and are responsible for mitotic quiescence and self-renewal properties while Δp63α sustain the stem cell proliferation potential. In order to validate these experimental markers in the normal human cornea, we studied their expression pattern in a large series of surgical specimens using immunohistochemistry. These data were further compared with the cytokeratin profile of the corneal and limbal epithelium.
Histologically normal human corneas were obtained from surgical specimens of 36 patients (age 7 m to 84 y) enucleated for uveal melanoma (16/36) or retinoblastoma (20/36) at the Hôpital Ophtalmique Jules-Gonin between 2000 and 2010. Clinical charts were reviewed for corneal disease. Paraffin sections were immunostained with antibodies against CEBPΔ, Bmi-1, BCRP/ABCG2, p63α, CK3, CK5, CK15, CK19 and Ki67.
In all specimens, C/EBPΔ and p63α were diffusely expressed in the nucleus of basal epithelial cells in the limbus but also in the central and peripheral cornea. By contrast, Bmi-1 expression was weak and restricted to the basal layer of the limbus. ABCG2/BCRP was demonstrated in basal cells of both limbus and cornea with an unexpected predominant nuclear staining. No correlation was found with patient's age, cytokeratin profile and proliferative index of the epithelium,
We studied the expression of functional stem cell markers ABCG2/BCRP, Bmi-1, p63α and C/EBPΔ in the normal human cornea and found that only Bmi-1 was always restricted to limbus while ABCG2/BCRP, p63α and C/EBPΔ were diffusely expressed in the corneal epithelium. These data show that caution should be exerted when extrapolating experimental data to normal human cornea.
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