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D. Gagen, S. Dieffenbaugher, M. Petrescu, C. W. Smith, Z. Li, A. R. Burns; Keratocyte Repopulation Following Corneal Epithelial Abrasion in the Mouse: A Role for ICAM-1. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5700.
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Mechanical injury to the corneal epithelium results in an inflammatory response whereby keratocytes beneath the site of injury undergo cell death. Previously we demonstrated keratocyte repopulation beneath the injured region in wildtype (WT) mouse cornea remains depressed up to 4 weeks after injury. ICAM-1, an extracellular surface adhesion molecule, is expressed on corneal epithelial cells, endothelial cells, and keratocytes. Mice deficient in ICAM-1 show delayed epithelial wound healing following central abrasion. In this study we wished to determine if ICAM-1 regulates keratocyte repopulation following epithelial abrasion.
Whole uninjured and injured right corneas from male C57Bl/6 WT mice and ICAM-1 null mice were immunostained with DAPI and a cocktail of FITC-conjugated leukocyte and dendritic-cell specific antibodies. Keratocyte nuclei were counted through the entire corneal thickness at central and paralimbal regions; FITC stained cells were excluded from the counts. Statistical analysis was performed with GraphPad Prism.
Baseline keratocyte densities in central and paralimbal regions of the ICAM-1 null and WT mouse cornea were similar. In both WT and ICAM-1 null mice, central epithelial abrasion resulted in early and complete loss of keratocytes from the anterior half of the central corneal stroma; paralimbal keratocytes were unaffected. 96h after injury, keratocyte repopulation was evident and total (anterior + posterior) central keratocyte numbers in the ICAM-1 null mouse cornea exceeded baseline values by 50%. In the anterior central region alone, keratocyte numbers recovered to baseline values in the ICAM-1 null cornea, while keratocyte recovery in WT corneas was incomplete (20% less than baseline). 2 weeks after injury, keratocyte numbers in anterior central region of ICAM-1 null corneas remained at baseline values while WT counts in the central anterior region remained depressed up to 4 weeks.
Enhanced keratocyte recovery following central epithelial abrasion in ICAM-1 null mice suggests ICAM-1 plays a negative regulatory role in keratocyte repopulation. Since ICAM-1 is expressed by a variety of corneal cells (epithelia, endothelia, and keratocytes), further studies are needed to define the cellular mechanism(s) by which ICAM-1 regulates keratocyte repopulation.
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