NDLI: Efficacy of VIP as Treatment for Bacteria-Induced Keratitis Against Multiple Pseudomonas aeruginosa Strains.

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Efficacy of VIP as Treatment for Bacteria-Induced Keratitis Against Multiple Pseudomonas aeruginosa Strains.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Berger, Elizabeth A. Carion, Thomas W. McWhirter, Cody R. Grewal, Daiyajot K.
Description	Country affiliation: United States Author Affiliation: Carion TW ( Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Michigan, United States.); McWhirter CR ( Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Michigan, United States.); Grewal DK ( Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Michigan, United States.); Berger EA ( Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Michigan, United States 2Department of Ophthalmology, Kresge Eye Institute, Detroit, Michigan, United States.)
Abstract	PURPOSE: Previous studies have demonstrated the efficacy of vasoactive intestinal peptide (VIP) treatment in regulating inflammation following bacterial keratitis induced by the P. aeruginosa strain 19660. However, in the current study we assessed whether disease outcome is specific to 19660 or if VIP treatment is effective against multiple P. aeruginosa strains. METHODS: B6 mice received daily IP injections of VIP from -1 through 5 days post injection (p.i.). Control mice were similarly injected with PBS. Corneal infection was induced using PA 19660, PAO1 or KEI 1025. Disease response was documented and bacterial plate counts and myeloperoxidase assays were performed. Expression of select inflammatory mediators as well as enzymes associated with lipid mediator production was assessed after VIP treatment. KEI 1025 was characterized by cytotoxicity and invasion assays and then confirmed for ExoS/ExoU expression. RESULTS: VIP treatment converted the susceptible response to resistant for the three P. aeruginosa strains tested. Disease response was significantly reduced with no corneal perforation. Anti-inflammatory mediators were enhanced after VIP treatment, while pro-inflammatory molecules were reduced compared to controls. Furthermore, VIP reduced inflammatory cell persistence in the cornea after infection with each of the P. aeruginosa strains. CONCLUSIONS: VIP treatment is effective at ameliorating disease pathogenesis for multiple P. aeruginosa strains, both cytotoxic and invasive. This study is also the first to indicate a possible role for VIP regarding lipid mediator expression in the eye. In addition, the clinical isolate, KEI 1025, was characterized as an invasive strain. Overall, this study strengthens the preclinical development of VIP as a therapeutic agent for ocular infectious disease.
ISSN	01460404
e-ISSN	15525783
DOI	10.1167/iovs.15-17315
Journal	Investigative Opthalmology & Visual Science
Issue Number	11
Volume Number	56
Language	English
Publisher	Association for Research in Vision and Ophthalmology
Publisher Date	2015-10-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Eye Infections, Bacterial Drug Therapy Keratitis Pseudomonas Infections Pseudomonas Aeruginosa Drug Effects Vasoactive Intestinal Peptide Therapeutic Use Animals Enzyme-linked Immunosorbent Assay Microbiology Intravitreal Injections Mice Mice, Inbred C57bl Real-time Polymerase Chain Reaction Administration & Dosage Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Discipline Ophthalmology
Content Type	Text
Resource Type	Article
Subject	Ophthalmology Sensory Systems Cellular and Molecular Neuroscience

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