June 2015
Volume 56, Issue 7
ARVO Annual Meeting Abstract  |   June 2015
Thrombomodulin protects against bacterial keratitis and is not angiogenic.
Author Affiliations & Notes
  • Linda D Hazlett
    Anatomy & Cell Biology, Wayne State Univ Sch of Med, Detroit, MI
  • Sharon A McClellan
    Anatomy & Cell Biology, Wayne State Univ Sch of Med, Detroit, MI
  • Cui Li
    Anatomy & Cell Biology, Wayne State Univ Sch of Med, Detroit, MI
  • Footnotes
    Commercial Relationships Linda Hazlett, None; Sharon McClellan, None; Cui Li, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 4053. doi:
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      Linda D Hazlett, Sharon A McClellan, Cui Li; Thrombomodulin protects against bacterial keratitis and is not angiogenic.. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4053.

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

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Purpose: Thrombomodulin (TMB), a cell surface glycoprotein composed of 5 domains, is expressed in a variety of cells. The N-terminal lectin-like domain (TMD1) interacts with Lewis Y antigen to inhibit angiogenesis and is responsible for TMB’s anti-inflammatory properties; it also binds high mobility group box-1 (HMGB1), preventing its deleterious effects, while domains 2 and 3 (TMD23) induce neovascularization, with response regression within 24 days. Despite data regarding activities of specific domains of TMB, nothing has been reported regarding testing its protective effects in experimental microbial keratitis, and whether it induces corneal vascularity which is the purpose of this study.

Methods: C57BL/6 mice were injected (subconjunctivally and i.p.) with recombinant (r)TMB and infected with P. aeruginosa. PBS controls were similarly treated. Clinical score, photography with a slit lamp, real time RT-PCR, MPO assay, and ELISA were used to assess the disease response.

Results: Data show that treatment of C57BL/6 mice with rTMB reduced clinical disease scores, corneal opacity and the neutrophil infiltrate. mRNA levels for IL-1β, MIP-2, TLR4, and RAGE were decreased, while anti-inflammatory molecules, including SIGIRR and ST2 levels were increased when compared with controls. ELISA confirmed the PCR data showing significant reduction of both IL-1β and MIP-2 protein level (3 and 5 days post infection) after rTMB treatment. VEGF, VEGF-R1 and VEGF-R2 were no different, or reduced after TMB (5 days p.i.).

Conclusions: TMB is protective in keratitis, reducing disease severity, and with no angiogenic effect .


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