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Friedrich E Kruse, Lorenz Latta, Leonard Holbach, Barbara Käsmann-Kellner, Berthold Seitz, Ursula Schlotzer-Schrehardt; The limbal epithelial stem cell niche in aniridia-related keratopathy. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3870. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
At present there are no histological data concerning the limbal anatomy in aniridia. Here, we investigate morphologic and molecular alterations in the limbal epithelial stem cell (LESC) niche in human congenital aniridia.
The blind and painful right eye of a 16-year old girl with congenital aniridia had to be enucleated because of uncontrolled intraocular pressure rise due to vitreous hemorrhage and luxation of the crystalline lens. The eye was vertically bisected and processed for routine histopathology, transmission electron microscopy, and immunohistochemistry.
Light microscopy showed an irregularly thickened corneal epithelium with abnormal stratification pattern, a weak and discontinuous basement membrane, absence of Bowman’s layer, subepithelial vascularized pannus and stromal inflammatory infiltration. In the limbal region, palisade structures were degraded and epithelial ridges were infiltrated by immune cells and displaced melanocytes. By electron microscopy, desmosomal structures and cytoplasmic keratin filaments were rarefied in the loosely adhering epithelial cells. By immunofluorescence, ocular surface epithelia were virtually negative for the corneal epithelial differentiation markers keratin 3 (K3) and K12, but uniformly positive for the conjunctival epithelial differentiation marker K13 in their superficial layers and for the proliferative basal cell markers K14, K15 and K19 in their basal layers, which connected with an abnormal basement membrane. Whereas normal nuclear expression patterns of p63α, Pax6 and Sox9 were observed in ocular surface cells, expression of desmosomal proteins, such as desmoglein, was reduced. Significantly increased staining for the proliferation marker Ki-67 could be observed throughout the entire surface epithelium. Although LESC markers, such as ABCG2 and N-Cadherin, were faintly expressed in some basal cells at the limbus, the normal niche architecture comprising specific matrix components and supporting cells like melanocytes was largely abolished.
These findings support the concept that alterations in the LESC niche architecture in aniridia are associated with disturbed differentiation of corneal epithelial cells and their gradual replacement by a conjunctival epithelial phenotype. In addition, enhanced cell proliferation rates indicating a chronic wound healing state may contribute to the pathogenesis of aniridia-related keratopathy.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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