April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Anti-Allergic Effects of Mapracorat, a Novel Selective Glucocorticoid Receptor Agonist, in Human Conjunctival Fibroblasts and Epithelial Cells
Author Affiliations & Notes
  • Megan E. Cavet
    Pharmaceutical R & D, Bausch + Lomb, Rochester, New York
  • Stepan M. Volhejn
    Pharmaceutical R & D, Bausch + Lomb, Rochester, New York
  • Karen L. Harrington
    Pharmaceutical R & D, Bausch + Lomb, Rochester, New York
  • Thomas Vollmer
    Pharmaceutical R & D, Bausch + Lomb, Rochester, New York
  • Keith W. Ward
    Pharmaceutical R & D, Bausch + Lomb, Rochester, New York
  • Jin-Zhong Zhang
    Pharmaceutical R & D, Bausch + Lomb, Rochester, New York
  • Footnotes
    Commercial Relationships  Megan E. Cavet, Bausch + Lomb (E); Stepan M. Volhejn, Bausch + Lomb (E); Karen L. Harrington, Bausch + Lomb (E); Thomas Vollmer, Bausch + Lomb (E); Keith W. Ward, Bausch + Lomb (E); Jin-Zhong Zhang, Bausch + Lomb (E)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 6422. doi:
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    • Get Citation

      Megan E. Cavet, Stepan M. Volhejn, Karen L. Harrington, Thomas Vollmer, Keith W. Ward, Jin-Zhong Zhang; Anti-Allergic Effects of Mapracorat, a Novel Selective Glucocorticoid Receptor Agonist, in Human Conjunctival Fibroblasts and Epithelial Cells. Invest. Ophthalmol. Vis. Sci. 2011;52(14):6422.

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

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Abstract

Purpose: : The aim of this study was to determine the ocular anti-allergic effects of mapracorat, a novel selective glucocorticoid receptor agonist (SEGRA) with corticosteroid-like anti-inflammatory activities and reduced transactivation-mediated side effects such as elevation of intraocular pressure, in human ocular cells.

Methods: : Two primary human conjunctival cell types, human conjunctival fibroblasts (HConF) and human conjunctival epithelial cells (HConEpiC), were challenged with IL-4 or IL-13 plus TNF-α and Luminex technology was used to determine the effects of mapracorat on the release of eotaxin and RANTES, two allergy-related chemokines, as well as proinflammatory cytokines. Dexamethasone (DEX) was used as the control.

Results: : IL-13 plus TNF-α in HConF significantly increased eotaxin-1, RANTES and numerous pro-inflammatory cytokines. Mapracorat significantly reduced IL-13 plus TNF-α-induced eotaxin-1, IL-6, IL-8, MCP-1 and RANTES release in a dose-dependent manner, having comparable efficacy to that of DEX. Significant inhibition was observed at 10 nM mapracorat. In HConEpiC, IL-4 plus TNF-α increased RANTES and multiple pro-inflammatory cytokines. Both mapracorat and DEX significantly reduced IL-4 plus TNF-α-induced RANTES, CTACK, GM-CSF, IL-6, IP-10 and MCP-1 release in a dose-dependent manner in this cell type. Inhibition was observed at a dose of 10 nM mapracorat for the majority of the induced chemokines/cytokines.

Conclusions: : Data from these in vitro models indicate that mapracorat is efficacious and potent in reducing IL-4 or IL-13 plus TNF-α-induced the release of allergy-related chemokines and proinflammatory cytokines from HConF and HConEpiC, supporting clinical evaluation of the compound in reducing allergic and inflammatory reactions in allergic conjunctivitis.

Keywords: conjunctiva • cytokines/chemokines • inflammation 
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