June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
HMGB1 antagonist, Box A reduces severity of Pseudomonas keratitis in susceptible C57BL/6 mice.
Author Affiliations & Notes
  • Sharon A McClellan
    Anatomy & Cell Biology, Wayne State Univ School of Med, Detroit, Michigan, United States
  • Linda Hazlett
    Anatomy & Cell Biology, Wayne State Univ School of Med, Detroit, Michigan, United States
  • Footnotes
    Commercial Relationships   Sharon McClellan, None; Linda Hazlett, None
  • Footnotes
    Support  This work was supported by grants R01EY016058, and P30EY004068 from the National Eye Institute, National Institutes of Health and by a Research to Prevent Blindness unrestricted grant to the Department of Ophthalmology, Kresge Eye Institute. Dr. Hazlett is the recipient of a 2012 Alcon Research award.
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 5761. doi:
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    • Get Citation

      Sharon A McClellan, Linda Hazlett; HMGB1 antagonist, Box A reduces severity of Pseudomonas keratitis in susceptible C57BL/6 mice.. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5761.

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

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Abstract

Purpose : High mobility group box 1 (HMGB1) contributes to poor disease outcome in P. aeruginosa keratitis. It functions as a chemoattractant and stimulates proinflammatory cytokine production. Box A is an antagonist for HMGB1 and has been reported to inhibit all its receptor dependent activities. The potential of Box A to protect susceptible C57Bl/6 (B6) mice from Pseudomonas keratitis is the purpose of this study.

Methods : Eyes of B6 mice were infected with P. aeruginosa ATCC strain 19660 and mice were treated subconjunctivally and intraperitoneally with Box A or PBS. Clinical scores, photography with a slit lamp camera, Real time RT-PCR, ELISA, MPO assay, and viable bacterial plate counts were used to assess the disease response.

Results : Treatment with Box A vs PBS improved disease in B6 mice at both 3 and 5 days postinfection (p.i.). Real time RT-PCR showed that Box A vs PBS treatment resulted in significantly less IL-1β, CXCL2, TLR4 and RAGE mRNA levels at 5 days p.i. ELISA analysis confirmed reduction in protein levels of IL-1β and CXCL2 at 5 days p.i. after Box A treatment, but no difference was detected between groups for TLR4 and RAGE. Box A also significantly reduced MPO values indicating a reduced neutrophil infiltrate at 3 and 5 days p.i. Consistent with this, bacterial plate counts were also significantly reduced in corneas of Box A vs PBS treated mice at 3 and 5 days p.i.

Conclusions : These data provide evidence that Box A significantly lessens the severity of Pseudomonas keratitis in susceptible B6 mice by decreasing IL-1β and CXCL2 that modulate the neutrophil infiltrate with a subsequent increase in bacterial killing. Results also confirm the role of HMGB1 in amplification of the inflammatory response.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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