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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)
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.
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.
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.
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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