June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Corneal wound healing mechanisms modulated by novel antimicrobial peptides
Author Affiliations & Notes
  • Anne Kasus-Jacobi
    Pharmaceutical Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
    Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
  • Amanda J. Stock
    Pharmaceutical Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
  • Gina L Griffith
    Ocular Trauma, United States Army Institute for Surgical Research, San Antonio, Texas, United States
  • H Anne Pereira
    Pharmaceutical Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
    Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
  • Footnotes
    Commercial Relationships   Anne Kasus-Jacobi, OUHSC (P); Amanda Stock, None; Gina Griffith, OUHSC (P); H Pereira, OUHSC (P)
  • Footnotes
    Support  NIH Grant EY026229-01A1, Oklahoma Center for the Advancement of Science and Technology (OCAST) Grant HR15-108
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 159. doi:
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    • Get Citation

      Anne Kasus-Jacobi, Amanda J. Stock, Gina L Griffith, H Anne Pereira; Corneal wound healing mechanisms modulated by novel antimicrobial peptides. Invest. Ophthalmol. Vis. Sci. 2017;58(8):159.

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

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Abstract

Purpose : Corneal abrasion is the most common eye injury. If corneal re-epithelialization is not optimal bacterial infection and vision loss can occur. The neutrophil protein CAP37 has wound healing and antimicrobial properties and our goal is to develop therapeutic peptides derived from CAP37 for the treatment of corneal abrasion and vision-threatening bacterial keratitis. This study was designed to identify membrane receptor(s) mediating the wound-healing effects of CAP37 and CAP37-derived bioactive peptides in corneal epithelial cells.

Methods : Corneal re-epithelialization was measured using a mouse corneal epithelium abrasion model, with and without treatment with CAP37 or derived peptides. To identify the receptors that mediate re-epithelialization induced by CAP37, we used an innovative ligand-based receptor capture method based on a TriCEPS reagent that features (1) an NHS group for coupling with the ligand protein, (2) a hydrazine cross-linker for coupling to the receptor, and (3) a biotin for purification of the complex. Interactions of CAP37 and its bioactive peptides with potential receptor candidates were then confirmed in vitro, using ELISA and far-dot-blotting analysis.

Results : We found that full-length CAP37 and CAP37-derived peptides based on a specific domain of the native CAP37 could accelerate corneal re-epithelialization in a mouse abrasion model. Using CAP37 coupled with TriCEPS on human corneal epithelial cells, we identified 17 proteins as most likely candidates to interact specifically with CAP37. Surprisingly, none of these candidates was a membrane receptor. Four potential candidates were tested in vitro for interaction with CAP37 and the calgranulin proteins S100-A8 and S100-A9 were confirmed to interact specifically and significantly with CAP37 and two of the bioactive peptides tested.

Conclusions : S100-A8 and S100-A9 are ligands of the receptor for advanced glycation end-products (RAGE) and are important players in ocular surface inflammatory diseases through the activation of Toll-like receptor 4 (TLR4). We speculate that a physical interaction of CAP37 and its peptides with S100-A8 and S100-A9 could modulate the activation of RAGE and/or TLR4 on corneal epithelial cells, thus promoting corneal wound healing. These findings will be key to optimization and translation of CAP37-derived peptides into innovative therapeutics with the dual effects of killing pathogens and promoting wound healing.

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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