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Sharon A. McClellan, Xiaoyu Jiang, Ronald P. Barrett, Yunfan Zhang, Megan E. Foldenauer, Linda D. Hazlett; Vasoactive Intestinal Peptide Modulates Growth Factors and their Receptors in Normal and Infected Cornea. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6137.
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Vasoactive intestinal peptide (VIP), an anti-inflammatory neuropeptide, down-regulates pro-inflammatory cytokines, and upregulates growth factors (GF), promoting healing in P. aeruginosa keratitis. Whether VIP is required for production of GF or their receptors in the cornea before and after infection is untested and the purpose of this study.
VIP-/- vs wild type C57BL/6 mice were infected and disease graded and recorded by slit lamp photography. PCR array was used to test fold differences in a panel (84 genes) of GF and their receptors in these mice. RT-PCR was used to confirm results for selected genes from the array. Immunostaining (IHC) was used to localize several GF and their receptors in the normal and infected eyes of C57BL/6 wild type and VIP-/- mice.
Infection in VIP -/- mice resulted in earlier [2 days postinfection (p.i.)] corneal perforation when compared to wild type mice in which perforation occurs at 5-7 days p.i. Thus, array and RT-PCR experiments were done in normal cornea and at 2 days p.i. In VIP-/- mice, GF receptors for EGF and HGF were significantly downregulated at 2 days p.i.; FGF receptor was similar between groups. GF, EGF and HGF were upregulated in VIP-/- while FGF was downregulated at 2 days p.i. IHC for GF and their receptors in the normal cornea of VIP-/- vs wild type mice, revealed less EGF, similar HGF, and more FGF epithelial staining. For GF receptors, more EGF and FGF, and less HGF epithelial staining was seen. At 1 day p.i., VIP-/- mice had more intense EGF, less HGF, and similar FGF staining vs wild type mice. For GF receptor staining, VIP-/- mice showed less intense EGF, HGF and FGF staining vs wild type mice.
The data reiterate the importance of VIP for healing in the infected cornea and provide new evidence that VIP is required for optimum GF and GF receptor production, particularly after infection.
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