Efficacy of VIP as Treatment for Bacteria-Induced Keratitis Against Multiple<i>Pseudomonas aeruginosa</i>Strains

Carion, Thomas W.; McWhirter, Cody R.; Grewal, Daiyajot K.; Berger, Elizabeth A.

doi:10.1167/iovs.15-17315

Cited by 17 publications

(14 citation statements)

References 28 publications

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“…Sample sizes were determined statistically prior to experimentation based on previous work [ 26 , 28 , 29 , 31 ], which includes a <5% mortality rate. Using a power analysis, we assume a mean difference = 2, standard deviation = 1, α = 0.05, power = 0.8, and a sample size ratio = 1.…”

Section: Methodsmentioning

confidence: 99%

Thymosin Beta-4 and Ciprofloxacin Adjunctive Therapy Improves Pseudomonas aeruginosa-Induced Keratitis

Carion

Ebrahim

Kracht

et al. 2018

Cells

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With increasing multidrug resistance and contraindication for corticosteroid use, the goal of this study was to develop thymosin beta-4 (Tβ4) as an adjunctive therapy to antibiotics for the treatment of bacterial keratitis that effectively promotes enhanced wound healing, host defense, and inflammation resolution. Disease outcome was assessed by clinical score, slit lamp photography, and histopathology. Cytokine profile, bacterial load, PMN infiltration, and Griess and reactive oxygen species (ROS) levels were determined. Adjunct Tβ4 treatment resulted in a significant improvement compared to PBS, Tβ4, and most remarkably, ciprofloxacin, correlating with changes in mediators of inflammation and wound healing. Collectively, these data provide evidence that wound healing is an essential aspect in the development of new therapies to treat corneal infection. Use of adjunctive Tβ4 provides a more efficacious approach for bacterial keratitis by addressing both the infectious pathogen and deleterious host response.

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Section: Methodsmentioning

confidence: 99%

Thymosin Beta-4 and Ciprofloxacin Adjunctive Therapy Improves Pseudomonas aeruginosa-Induced Keratitis

Carion

Ebrahim

Kracht

et al. 2018

Cells

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“…After that, they were centrifuged and washed in PBS to remove bacterial metabolic residues present in the medium and that could interfere in the experiment. They were then resuspended in PBS at a concentration of approximately 1x10 6 CFU / ml, and 5ul of the solution were used for ocular inoculation [33][34][35][36][37].…”

Section: Preparation Of Bacteria For Inoculationmentioning

confidence: 99%

Evaluation of Annexin A1 Protein in an Infectious Keratitis Model: Therapeutic Perspectives

Silva

Hamade

Silva

et al. 2019

CTOY

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Introduction: bacterial keratitis caused by Pseudomonas aeruginosa is one of the causes of blindness in the world, due to pathogenicity of the bacteria that can lead to corneal perforation. Studies on the protein annexin A1 (AnxA1) point it as one of the essential mediators in homeostasis of inflammation and ocular infections. However, there are no known reports of AnxA1 in keratitis. Objetive: to investigate the expression profile of AnxA1 in the P. aeruginosainduced keratitis model in two strains of mice (susceptible and pathogen resistant).Method: for the development of experimetal keratitis, the mice had their right eyes ulcerated and immediately inoculated with 5 μl of P. aeruginosa in PBS. The animals were euthanized after 24 hours of the bacteria inoculation. The eyes were clinically evaluated and histopathologically processed for quantitative analyses of the inflammatory infiltrate and immunohistochemical studies of the expressions of the AnxA1 and the receptor for formylated peptides (fpr2).Results: our results demonstrated a higher influx of inflammatory cells, mainly neutrophils in the susceptible animals (C57BL / 6) compared to those considered resistant (BALB / c) and controls. Immunohistochemical studies indicated weak expression of AnxA1 and fpr2 in the anterior epithelium and stroma of the cornea. However, after keratitis induction, overexpression of AnxA1 and fpr2 occurred in the corneas of both mice strains. Furthermore, greater expression of AnxA1 in the anterior corneal epithelium was observed in the C57BL / 6 animals.Conclusions: AnxA1 and fpr2 may be related to infectious keratitis induced by P.aeruginosa, which stimulates further investigations on the use of AnxA1 as a possible coadjuvant therapeutic strategy in bacterial keratitis.

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“…We realize that there is a possibility that the genomic sequence for exoU in these clinical isolates is different enough from the reference ATCC strain, that primer annealing and PCR amplification do not effectively occur. However, others have reported success when using a single set of primers to amplify exoU [ 38 , 39 , 40 ]. In this regard, Berthelot et al [ 40 ] have shown that expression of exoS and exoU were prevalent in 92 epidemiologically unrelated isolates of P. aeruginosa .…”

Section: Discussionmentioning

confidence: 99%

Characterization of Three Ocular Clinical Isolates of P. aeruginosa: Viability, Biofilm Formation, Adherence, Infectivity, and Effects of Glycyrrhizin

et al. 2017

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We selectively characterized three isolates from Pseudomonas aeruginosa keratitis patients and how glycyrrhizin (GLY) affected them. Type III toxins were determined using polymerase chain reaction (PCR). Minimum Inhibitory Concentration (MIC) of GLY and assays for its effects on: time kill, bacterial permeability, and biofilm/adhesion were done. In vivo, C57BL/6 (B6) mice were treated topically with GLY after G81007 infection. Clinical score, photography with a slit lamp and RT-PCR were used to assess treatment effects. Isolates expressed exoS and exoT, but not exoU. MIC for all isolates was 40 mg/mL GLY and bacteriostatic effects were seen for G81007 after treatment using time kill assays. From viability testing, GLY treatment significantly increased the number of permeabilized bacteria (live/dead assay). Isolates 070490 and G81007 formed more biofilms compared with R59733 and PAO1 (control). GLY-treated bacteria had diminished biofilm compared with controls for all isolates. GLY reduced adherence of the G81007 isolate to cultured cells and affected specific biofilm associated systems tested by reverse transcription PCR (RT-PCR). In vivo, after G81007 infection, GLY treatment reduced clinical score and messenger RNA (mRNA) expression of IL-1β, TNF-α, CXCL2 and HMGB1. This study provides evidence that GLY is bacteriostatic for G81007. It also affects biofilm production, adherence to cultured cells, and an improved keratitis outcome.

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Efficacy of VIP as Treatment for Bacteria-Induced Keratitis Against MultiplePseudomonas aeruginosaStrains

Cited by 17 publications

References 28 publications

Thymosin Beta-4 and Ciprofloxacin Adjunctive Therapy Improves Pseudomonas aeruginosa-Induced Keratitis

Thymosin Beta-4 and Ciprofloxacin Adjunctive Therapy Improves Pseudomonas aeruginosa-Induced Keratitis

Evaluation of Annexin A1 Protein in an Infectious Keratitis Model: Therapeutic Perspectives

Characterization of Three Ocular Clinical Isolates of P. aeruginosa: Viability, Biofilm Formation, Adherence, Infectivity, and Effects of Glycyrrhizin

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