July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
VIP Treatment Mediates LTB4-BLT1 Axis in Pseudomonas aeruginosa Induced Keratitis
Author Affiliations & Notes
  • Thomas W Carion
    Anatomy and Cell Biology, Wayne State School of Medicine, Detroit, Michigan, United States
  • David J Kracht
    Anatomy and Cell Biology, Wayne State School of Medicine, Detroit, Michigan, United States
  • Elizabeth A Berger
    Anatomy and Cell Biology, Wayne State School of Medicine, Detroit, Michigan, United States
    Ophthalmology, Kresge Eye Institute, Detroit, Michigan, United States
  • Footnotes
    Commercial Relationships   Thomas Carion, None; David Kracht, None; Elizabeth Berger, None
  • Footnotes
    Support  NIH Grant R01 EY023226, Research To Prevent Blindness, NIH Grant P30 EY004068
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 1548. doi:
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    • Get Citation

      Thomas W Carion, David J Kracht, Elizabeth A Berger; VIP Treatment Mediates LTB4-BLT1 Axis in Pseudomonas aeruginosa Induced Keratitis. Invest. Ophthalmol. Vis. Sci. 2018;59(9):1548.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose : Leukotrienes are potent mediators essential to inflammation. LTB4 is a classical chemoattractant known to activate granulocytes and bind the major receptors BLT1 (high affinity receptor) and BLT2 (low affinity receptor). The LTB4-BLT1 axis plays an important role in the immune pathway. However, unregulated activation of this circuit can lead to a state of prolonged, chronic inflammation. Vasoactive intestinal peptide (VIP) is known to improve the disease response in a mouse model of bacterial keratitis. This study focuses on the immunoregulatory effects of VIP regarding the LTB4-BLT1 axis as a mechanism of action for improved disease outcome.

Methods : Pseudomonas aeruginosa (PA)-induced keratitis was carried out in B6 mice. Infected corneas were treated with either VIP, ciprofloxacin (cipro) or VIP+cipro and compared to PBS-treated B6 controls. Disease response was assessed by mean clinical score, real-time RT-PCR, ELISA and flow cytometry. Inflammatory cells and corneal epithelial cells were further examined in vitro using PA stimulation assays.

Results : VIP+cipro treatment significantly improved disease outcome in B6 mice compared to all other treatment groups. This response was associated with a significant reduction in infiltrating PMN, accompanied by reduced BLT1 receptor expression and LTB4 production. In addition, the rate limiting enzyme 5-LOX was reduced after VIP+cipro treatment compared to PBS controls. Similar trends were observed in VIP only treated mice, but VIP+cipro more effectively decreased bacterial load. In vitro results further elucidated how VIP influences the LTB4-BLT1 circuit in PMN, macrophages and corneal epithelial cells.

Conclusions : As the first study to examine the LTB4-BLT1 axis in a model of bacterial keratitis, our results indicate that VIP modulates this key chemotactic pathway. Surprisingly, previous studies have shown that inhibition of LTB4 production or blockage of BLT1 by pharmacological inhibitors have had little success in treating different inflammatory diseases. In our study, VIP treatment appears to be modulating this interaction as opposed to inhibiting it, whereby sufficient LTB4-BLT1 interaction takes place, allowing for PMN infiltration into the infected cornea to properly phagocytose and kill the bacteria. Overall, VIP treatment effectively decreases 5-LOX, LTB4 and BLT1 over time allowing for immune homeostasis and tissue restoration in the cornea.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.


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