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T. Nagasaki, J. Zhao; The Stable and Ectopic Presence of Conjunctival Epithelial Stem Cells in a Conjunctivalized Cornea . Invest. Ophthalmol. Vis. Sci. 2005;46(13):2079.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Limbal destruction has been known to trigger conjunctivalization of the corneal surface. This study was initiated to determine whether epithelial homeostasis in a conjunctivalized cornea is maintained by the presence of conjunctival epithelial stem cells. Methods: Ubiquitous GFP mice were used. The limbal epithelium was removed in the entire circumference and the injury was allowed to heal naturally, which lead to conjunctivalization of the corneal surface. Epithelial cell movement in a conjunctivalized cornea was determined by monitoring epithelial GFP patterns by in vivo time–lapse fluorescence microscopy. The presence of stem cells was determined by mapping label–retaining cells (LRCs) in whole–mounts after pulse–chase with bromodeoxyuridine (BrdU). In the first experiment, newborn mice were pulse–labeled with BrdU for 4 days, and at 6 weeks the conjunctivalization was triggered by limbal destruction. Animals were sacrificed 2 weeks later to determine LRCs in the conjunctivalized cornea. In the second experiment, the animals, whose cornea had been conjunctivalized for at least 10 weeks, were pulse–labeled with BrdU for 2 weeks, followed by a chase of >8 weeks to determine LRCs in the conjunctivalized cornea. Results: Epithelial GFP patterns in a conjunctivalized cornea were stationary for at least 20 weeks, and much longer in some occasions, suggesting that epithelial cells were generally immobile in a lateral direction. Labeling with BrdU demonstrated that stationary GFP positive cells were mitotically active, suggesting that they were capable of self–renewal in situ. In normal ocular surface, LRCs were present in the conjunctiva and the limbus, but absent in the cornea. After total conjunctivalization of the cornea, however, LRCs were now found throughout the cornea proper, suggesting that conjunctival LRCs migrated to the cornea during corneal resurfacing. Corneal LRCs could be also demonstrated by BrdU pulse–chase with corneas that had been conjunctivalized for at least 10 weeks. Taken together, these results suggest that epithelial homeostasis of conjunctivalized cornea is maintained by stationary conjunctival epithelial stem cells. Conclusions: Conjunctivalization of the cornea is associated with stable, ectopic presence of conjunctival epithelial stem cells, suggesting that conjunctival stem cells and their niches can establish their presence in the corneal environment and continue to express their native, non–corneal phenotype. Thus, eradication of conjunctivalization–associated pathology may require removal of conjunctival epithelial stem cells from the cornea.
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