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Edgar M Espana, David E Birk, mei sun; Collagen XII Influences Corneal Endothelial Maturation and Function. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2575.
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© ARVO (1962-2015); The Authors (2016-present)
The objective of this study is to demonstrate the presence and location of corneal endothelial progenitor cells and the influence of collagen XII deficiency on the maturation and function of the corneal endothelium.
Corneal preparations were used to study the expression of progenitor cell markers. Nestin and nerve growth factor receptor p75 (NGFR), as well as a proliferation marker Ki-67, were examined in wild type and Col12a1(-/-) mice. Mice also were pulsed with 5-bromo-2'-deoxyuridine (BrdU) injected intraperitoneally and chased for 1 and 3 weeks. Fluorescence Recovery after Photobleaching (FRAP) and connexin 43 immunocharacterization was also performed to evaluate gap junctions and intercellular communications.
Reactivity against BrdU was found in the central and peripheral cornea at 1 week, and was found exclusively at the extreme endothelial periphery 3 weeks following a BrdU pulse. Nestin and NGFR were homogeneously expressed in all corneal cell layers in the immature WT cornea (P3), but were down regulated during corneal maturation, with minimal or no expression present in the mature P90 central cornea. Nestin and NGFR expression in the central cornea persisted longer in Col12a1(-/-) corneas. Endothelial cells became quiescent at P10 in WT but proliferating cells were noted until P16 in Col12a1(-/-) mice. The pattern of FRAP, in mature WT mice showed rapid fluorescein recovery suggestive of normal endothelial to endothelial cell communications. In contrast, Col12a1(-/-) corneas had a severe delay in fluorescein recovery that was associated with a decreased expression of connexin 43.<br />
During early postnatal life, corneal endothelium is composed of replicating cells expressing progenitor markers, i.e., NGFR, nestin. In contrast, in the mature endothelium slow cycling cells, and cells expressing progenitor markers are restricted to the extreme corneal periphery. Collagen XII, however, delays normal endothelial maturation and persistence of proliferating cells that express progenitor markers is found in Col12a1(-/-) corneas. The mechanism by which Collagen XII delays maturation can be impairment of cell-cell communications.
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