July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Characterization and Role of KCa3.1 Ion Channel in Corneal Wound Healing and Fibrosis
Author Affiliations & Notes
  • Lindsey McDaniel
    Ophthalmology, Harry S. Truman Memorial Veteran Hospital, Columbia, Missouri, United States
    Mason Eye Institute, University of Missouri School of Medicine, Columbia, Missouri, United States
  • Suneel Gupta
    Ophthalmology, Harry S. Truman Memorial Veteran Hospital, Columbia, Missouri, United States
    Veterinary Medicine and Surgery , Veterinary School, Columbia, Missouri, United States
  • Michael K Fink
    Ophthalmology, Harry S. Truman Memorial Veteran Hospital, Columbia, Missouri, United States
    Veterinary Medicine and Surgery , Veterinary School, Columbia, Missouri, United States
  • Nathan Hesemann
    Ophthalmology, Harry S. Truman Memorial Veteran Hospital, Columbia, Missouri, United States
    Mason Eye Institute, University of Missouri School of Medicine, Columbia, Missouri, United States
  • Prashant R Sinha
    Ophthalmology, Harry S. Truman Memorial Veteran Hospital, Columbia, Missouri, United States
    Veterinary Medicine and Surgery , Veterinary School, Columbia, Missouri, United States
  • Sally Heil
    Veterinary Medicine and Surgery , Veterinary School, Columbia, Missouri, United States
  • Hannah B Gafen
    Ophthalmology, Harry S. Truman Memorial Veteran Hospital, Columbia, Missouri, United States
    Veterinary Medicine and Surgery , Veterinary School, Columbia, Missouri, United States
  • Douglas K Bowles
    Biomedical Sciences, University of Missouri- College of Veterinary Medicine, Columbia, Missouri, United States
  • Rajiv R Mohan
    Ophthalmology, Harry S. Truman Memorial Veteran Hospital, Columbia, Missouri, United States
    Veterinary Medicine and Surgery , Veterinary School, Columbia, Missouri, United States
  • Footnotes
    Commercial Relationships   Lindsey McDaniel, None; Suneel Gupta, None; Michael Fink, None; Nathan Hesemann, None; Prashant Sinha, None; Sally Heil, None; Hannah Gafen, None; Douglas Bowles, None; Rajiv Mohan, None
  • Footnotes
    Support  The Ruth M. Kraeuchi Missouri Endowed Chair Ophthalmology Fund (RRM), and partial support from the NIH/NEI R01EY017294 (RRM) and Veterans Health Affairs 1I01BX00357 (RRM) grants.
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 4334. doi:
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    • Get Citation

      Lindsey McDaniel, Suneel Gupta, Michael K Fink, Nathan Hesemann, Prashant R Sinha, Sally Heil, Hannah B Gafen, Douglas K Bowles, Rajiv R Mohan; Characterization and Role of KCa3.1 Ion Channel in Corneal Wound Healing and Fibrosis
      . Invest. Ophthalmol. Vis. Sci. 2018;59(9):4334.

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

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Abstract

Purpose : We sought to study the role of intermediate-conductance Ca2+-activated K+ channels (KCa3.1) corneal wound healing and fibrosis management using transgenic KCa3.1 knockout mouse in vivo and human cornea in vitro.

Methods : Donor human corneas, human corneal epithelial, fibroblast and endothelial cells, and blackC57 wild type and KCa3.1knockout mice were used to characterize expression of KCa3.1 in the cornea. Quantitative RT-PCR, Western blotting, scratch assay, and immunofluorescence, and TRAM-34 (selective KCa3.1 inhibitor) were used to study the role of KCa3.1 in corneal wound healing and fibrosis treatment. Corneal fibrosis in human cornea in vitro was produced by TGFb1 and in vivo in mouse cornea by alkali-injury. Cytotoxicity of TRAM-34 was tested with trypan blue assay.

Results : Substantial KCa3.1 gene and protein levels were detected in all three major layers of the human cornea. The corneas of KCa3.1 deficient mice demonstrated significantly reduced expression of profibrotic genes, collagen-I, collagen IV and alpha smooth muscle actin (αSMA), compared to wild type mice. The eyes of age- and sex-matched KCa3.1-/- mice showed reduced corneal opacification in live animals and myofibroblast cells in corneal tissues in vivo at 3, 7 and 14 days after alkali-injury compared to the KCa3.1-/- mice. A selective KCa3.1 inhibitor, TRAM-34, significantly inhibited TGFβ1-induced migration (P <0.01) and transdifferentiation of HCF to myofibroblasts (P <0.001). Additional, studies characterizing role of KCa3.1 in corneal fibrosis are underway.

Conclusions : KCa3.1 modulates corneal wound healing and may potentially offer an innovative approach for controlling corneal fibrosis in vivo.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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