Clusters of Corneal Epithelial Cells Reside Ectopically in Human Conjunctival Epithelium

Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kioto, Kyōto, Japan
Investigative Ophthalmology & Visual Science (Impact Factor: 3.4). 05/2006; 47(4):1359-67. DOI: 10.1167/iovs.05-1084
Source: PubMed


The ocular surface is covered by two biologically distinct epithelia: corneal and conjunctival. The expression of keratin12 (K12) is currently considered a hallmark of cornea-type differentiation. In the current study, the biological features of K12-positive cells in human bulbar conjunctival epithelium were examined.
Human conjunctival tissues were subjected to investigate the K12-positive cells in conjunctiva by immunostaining, in situ hybridization, Western blot analysis, reverse transcriptase-polymerase chain reaction (RT-PCR), and fluorescence-activated cell sorting (FACS). Gene expression profiling of these cells was performed with introduced amplified-fragment length polymorphism (iAFLP). To determine the presence of stem- or progenitor cells, immunostaining and colony-forming assays were performed.
Western blot analysis, RT-PCR revealed that K12 was expressed in conjunctival epithelium. Immunostaining analysis showed that K12-positive cells reside mainly in clusters in conjunctival epithelium. FACS analysis showed that 0.2% to 1.7% of conjunctival epithelial cells collected from the inferior bulbar conjunctiva were K12 positive. iAFLP analysis revealed that the gene expression patterns of these cells were highly similar to that of corneal epithelial cells. p63 and ABCG2 were expressed beneath the K12-positive cells. Some colony-forming cells expressed K12.
The K12-positive cells appear to be ectopically residing, self-maintaining corneal epithelial cells in the conjunctival epithelium.

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    • "This phenomenon is similar to Kawasaki et al.’s finding that keratin 12-positive corneal epithelial cells can ectopically reside in the conjunctival epithelium. The researchers found that between 0.2% and 1.7% of the conjunctival epithelial cells collected from the inferior bulbar conjunctiva were keratin 12 positive [34]. Although these keratin 12-positive cells may directly extend from the limbus, they may be maintained by their own stem or progenitor cells in the conjunctiva. "
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    • "Last but not least, as previously shown by Ang et al. [13], the human CjE cells have acquired the tonofilament pattern that characterizes the corneal epithelial cells, the expression of CK3 and CK12. With respect to CK12, gene expression comparisons by microarray [19] and histology have shown that certain areas of the human CjE the epithelium may spontaneously express a substantial level of the CK12 mRNA [20]. However, no such observation has been made in regard to CK3. "
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    • "These cytokeratins are the hallmark of corneal differentiation and are rarely reported in conjunctival cells. The presence of clusters of corneal progenitor cells in conjunctiva has been reported, and it is possible that the expression of K3 and K12 observed in this study could be due to the proliferation of corneal stem cells in conjunctiva [34]. It is also possible that these differences are due to the different niches that the culture conditions used here provide and thereby lead to changes in the expression profile. "
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