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Alan Burns, Qiong Liu, Zhijie Li, Clifton Smith; Mast Cells and the Inflammatory Response to Corneal Epithelial Abrasion. Invest. Ophthalmol. Vis. Sci. 2013;54(15):3912. doi: https://doi.org/.
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Inflammation is beneficial to corneal epithelial and nerve regeneration following abrasion injury. Numerous studies have documented a regulatory role for mast cells in inflammation, tissue regeneration and wound healing. The mast cell contribution to inflammation and wound healing after epithelial abrasion is unknown.
Anesthetized adult wildtype C57BL/6 mice or mast cell deficient mice (c-kit-/-) received a 2.0 mm diameter central corneal epithelial abrasion using a golf-club spud. To inhibit mast cell degranulation, wildtype mice were pretreated with cromoglycate (orally, topically or intraperitoneally) or ketotifen (topically). For all mice, topical application of fluorescein was used to evaluate the rate of epithelial wound closure. Excised corneal whole mounts were prepared for immunofluorescence microscopy and used to evaluate changes in limbal vessel diameter, numbers of extravasated platelets and neutrophils and numbers of dividing epithelial cells.
Mast cells were abundant near limbal vessels in wildtype mice, but rarely seen in c-kit-/- mice. In wildtype mice, epithelial abrasion induced an acute inflammatory response with early (3h) and sustained (out to 30h) dilation in the limbal vessels, and significant neutrophil and platelet extravasation. Mice deficient in mast cells (c-kit -/-) exhibited early vessel dilation (3h), but this response was not sustained. These mice also showed diminished platelet and neutrophil recruitment which was accompanied by delayed (6h) epithelial wound closure and significant blunting of basal epithelial cell division (60% less at 18h post-injury). Neutrophil recruitment was partially restored in mast cell deficient mice that received a subconjunctival injection of cultured wildtype mast cells 4 days prior to epithelial abrasion. Experiments treating wildtype mice with cromolyn or ketotifen gave results consistent with those in c-kit -/- mice.
Collectively, the data suggest mast cells play a pivotal role in corneal inflammation and wound healing. Specifically, mast cells are needed for sustained limbal vessel dilation and coordinated neutrophil and platelet recruitment. In the absence of mast cells or their degranulation products, the diminished leukocyte recruitment likely accounts for the observed reduction in the rate of corneal wound closure and the number of dividing epithelial cells.
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