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Xiaoyu Jiang, Sharon A. McClellan, Ronald P. Barrett, Elizabeth A. Berger, Yunfan Zhang, Linda D. Hazlett; VIP and Growth Factors in the Infected Cornea. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1207.
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Vasoactive intestinal peptide (VIP) is an anti-inflammatory neuropeptide that down-regulates pro-inflammatory cytokines and promotes healing in a model of P. aeruginosa keratitis. Growth factors also play a role in corneal healing and restoration of tissue homeostasis after wounding. However, whether VIP treatment modulates growth factors to promote healing in the infected cornea remains untested and is the purpose of this study.
C57BL/6 (B6) mice were injected with VIP and mRNA and protein levels and immunostaining of EGF, FGF, HGF and VEGF-A were tested. Exogenous treatment with a mixture of the growth factors also was done and levels of cytokines, defensins and bacterial counts were determined.
Real-time RT-PCR, immunostaining and ELISA data demonstrated that treatment with VIP enhanced levels of EGF, FGF, and HGF during disease; and that VEGF-A, and associated angiogenic molecules also were increased by VIP. Moreover, immunohistochemical studies confirmed that both epithelial and stromal cells participated in growth factor production. Most notably, treatment with a mixture of EGF, FGF and HGF after disease onset, prevented corneal perforation, when compared with controls. This outcome was associated with down-regulation of pro-inflammatory cytokines such as MIP-2, up-regulation of anti-inflammatory cytokines such as TGF-ß and anti-microbials ß defensins 2 and 3, as well as decreased plate counts at 1 (p=0.0001) and 5 (but not significantly, p=0.09) days p.i.
Collectively, the data provide evidence that VIP modulates growth factor and angiogenic molecule levels in the infected cornea and that this in turn promotes healing and restoration of tissue homeostasis.
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