June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Topical glycyrrhizin is therapeutic for Pseudomonas aeruginosa keratitis.
Author Affiliations & Notes
  • Sandamali Amarasingha Ekanayaka
    Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Michigan, United States
  • Sharon A McClellan
    Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Michigan, United States
  • Ronald P Barrett
    Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Michigan, United States
  • Linda Hazlett
    Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Michigan, United States
  • Footnotes
    Commercial Relationships   Sandamali Amarasingha Ekanayaka, None; Sharon McClellan, None; Ronald Barrett, None; Linda Hazlett, Wayne State University (P)
  • Footnotes
    Support  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.
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 4290. doi:
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    • Get Citation

      Sandamali Amarasingha Ekanayaka, Sharon A McClellan, Ronald P Barrett, Linda Hazlett; Topical glycyrrhizin is therapeutic for Pseudomonas aeruginosa keratitis.
      . Invest. Ophthalmol. Vis. Sci. 2017;58(8):4290.

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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 Pseudomonas (P.) aeruginosa keratitis. Glycyrrhizin (GLY), a small molecule inhibitor of HMGB1 given prophylactically (subconjunctivally and intraperitoneally), reduced HMGB1 levels and protected against keratitis. However, the therapeutic potential of GLY has not been tested and is the purpose of this study.

Methods : C57BL/6 mice (B6) were infected with a non-cytotoxic clinical isolate (KEI 1025) of P. aeruginosa and treated 6 hours after infection with GLY or PBS topically. Clinical scores, photography with a slit lamp, ELISA, MPO assay, bacterial plate counts, histopathology, reactive oxygen/nitrogen species (ROS/RNS) and in vitro macrophage (Mφ) polarization assays were used to assess the effects of GLY treatment. In separate similar experiments, the synergistic potency of GLY with Tobramycin (Tob) at 6 hours after infection was assessed using B6 mice infected with KEI 1025.

Results : GLY vs PBS topical treatment improved disease outcome with significantly reduced clinical scores. Pro-inflammatory protein levels (HMGB1, RAGE, TLR4, TNF-α and CXCL2), neutrophil infiltrate, bacterial plate count and ROS/RNS levels were reduced significantly after GLY treatment. Consistent with these data, using in vitro assays, GLY promoted M2 phenotypic switching of LPS stimulated Mφs. Synergy experiments showed a significantly reduced bacterial plate count in GLY+Tob treated mice compared to PBS, GLY or Tob controls.

Conclusions : GLY treatment initiated 6 hours after infection is therapeutic for P. aeruginosa keratitis and when combined with tobramycin treatment, synergism is observed.

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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