Purchase this article with an account.
Elizabeth Berger, Linda Hazlett; VIP Treatment of Bacterial Keratitis Against Multiple Pseudomonas Strains. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5216.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Studies from our laboratory have demonstrated the efficacy of vasoactive intestinal peptide (VIP) treatment in regulating inflammation following bacterial keratitis induced by P. aeruginosa (PA) ATCC strain 19660. However, we assessed whether these effects are specific to 19660 (a cytotoxic strain) or if VIP treatment would be just as effective against multiple strains of PA. As such, two additional strains were tested - PAO1 (ATCC 15692), an invasive strain and KEI 1025, a clinical isolate.
C57BL/6 (B6) mice received daily IP injections of VIP (5 nM in 100 μL) from -1 through 7 days p.i. Control mice were similarly injected with PBS. Mice were infected with PA 19660, PAO1 or KEI 1025. Whole corneas were graded by clinical score and disease response was documented using a slit-lamp. Real-time RT-PCR and ELISA were used to assess the effects of VIP treatment on cytokine/chemokine production and enzymes associated with specialized pro-resolving mediator (SPM) production. Bacterial plate counts, MPO and Greiss assays were performed to examine host inflammatory cell function.
VIP treatment converted the susceptible response to resistant for all three strains of PA tested. Clinical scores were significantly improved and corneal perforation was averted. Further analysis revealed that corneas of VIP treated mice had significantly increased levels for TGF-β and IL-10; while pro-inflammatory molecules (IL-1β, TNF-α and CXCL2) were significantly down-regulated when compared to controls. Furthermore, enzymes associated with SPM formation (12-LOX, 15-LOX, COX-2) were disparately expressed after VIP treatment against PA 19660, PAO1 and KEI 1025 compared to PBS treated animals.
VIP treatment is effective at ameliorating disease pathogenesis for all three PA strains tested as indicated by cytokine/chemokine expression and host inflammatory cell function. In addition, this study is the first to indicate a possible role for VIP in driving SPM expression and subsequent disease resolution. In summary, the data from this study further strengthen the preclinical development of VIP as a therapeutic for ocular infectious disease.
This PDF is available to Subscribers Only