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Mary Ann Stepp, Daniel R Saban, Sonali Pal Ghosh, Ahdeah Pajoohesh-Ganji, Gauri Tadvalkar, Christophe Cataisson, A Sue Menko; Resolving wounds induce a more robust cytokine mRNA response and recruitment of larger numbers of neutrophils. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4726.
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To determine the mechanism underlying the failure of debridement wounds made to the mouse cornea to fully resolve 4 weeks after wounding.
BALB/c mice were used for 1.5 mm manual corneal wound healing studies using a dulled blade or a rotating burr. After wounding, mice were allowed to heal for 3 or 18 hrs. After sacrifice, epithelial tissues, whole corneas, or denuded stromas were pooled from 6 corneas per variable; a minimum of 4 different pooled samples were used to either purify RNA for QPCR or to perform flow cytometry to quantify leukocyte populations.
As soon as 3 hr after wounding dramatic increases in numerous cytokine and inflammation-associated mRNAs can be observed. Significant increases are seen after rotating burr compared to dulled blade woulds in RNA isolated from epithelial tissues for IL1α and from wounded whole corneas for IL36A, Cox-2, and MMP9. These differences predict that an increase in leukocyte recruitment in rotating burr wounded corneas would emerge over time after wounding. Flow cytometry studies performed 18 hr after dulled blade and rotating burr wounds showed significantly elevated recruitment of neutrophils but not monocytes after rotating burr wounds. While IL36A levels remain elevated in RNA isolated from rotating burr wounded epithelial and stromal tissues 18 hr after wounding, IL1α and MMP9 levels are no longer significantly different between wound types. In contrast to 3 hr, by 18 hr, Cox-2 and CXCL1 levels are significantly elevated in dulled blade wounded corneas.
Rotating burr wounds induce a more robust induction of cytokine and inflammation associated mRNAs than do dulled blade wounds and these differences induce more neutrophils to be recruited into the cornea 18 hr after rotating burr wounds and, over time, lead to wound resolution. Cytokine-mediated signaling plays a positive role in inducing wound resolution after debridement wounding in the cornea.
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