April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
P-Glycoprotein Blockers Potentiate the Effect of Mitomycin C on Human Tenon Fibroblasts
Author Affiliations & Notes
  • Andrew J. White
    Department of Ophthalmology, Westmead Hospital, Sydney, Australia
  • Elizabeth Kelly
    Cellular Molecular Pathology Research Unit,
    University of Sydney, Sydney, Australia
  • Paul R. Healey
    Department of Ophthalmology, Westmead Hospital, Sydney, Australia
    Centre for Vision Research, Westmead Millennium Institute,
    University of Sydney, Sydney, Australia
  • Hans Zoellner
    Cellular Molecular Pathology Research Unit,
    University of Sydney, Sydney, Australia
  • Footnotes
    Commercial Relationships  Andrew J. White, None; Elizabeth Kelly, None; Paul R. Healey, None; Hans Zoellner, None
  • Footnotes
    Support  Westmead Millenium Scholarship
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 3113. doi:https://doi.org/
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      Andrew J. White, Elizabeth Kelly, Paul R. Healey, Hans Zoellner; P-Glycoprotein Blockers Potentiate the Effect of Mitomycin C on Human Tenon Fibroblasts. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3113. doi: https://doi.org/.

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

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Abstract

Purpose: : Mitomycin C is frequently used to retard wound healing after glaucoma surgery. High dose Mitomycin C substantially increases toxicity-related complications. There is potential benefit from either replacement of Mitomycin C or adjunctive use of agents that increase its therapeutic activity when used at a low dose. We investigated the effect upon Mitomycin C induced apoptosis of agents inhibiting channel p-glycoprotein activity in primary human tenon fibroblast cell culture.

Methods: : Fibroblast cell lines were established by explant culture from human tissue biopsy samples obtained during trabeculectomy procedures. Cells were exposed to mitomycin C at varying concentrations (0.01 - 0.4 mg/ml) for 3 minutes, prior to washing in the presence or absence of the following drugs: Staurosporine (0.003mg/ml); Verapamil (2.5 - 0.25mg/ml); or cyclosporine (50 - 0.5mg/ml). All are thought to bind and inhibit activity of P-gp for separate P-gp substrates. Following exposure, cells were cultured for 6 Hrs and surviving cells counted using a haemocytometer.

Results: : Both verapamil and staurosporine exhibited mild toxic effects on their own but greatly enhanced the apoptotic effect of Mitomycin C. Low doses of verapamil were used to mimic a clinically acceptable dose administered topically. Doses as low as 0.25mg/ml verapamil continued to show significant augmentation of the apoptotic effect of mitomycin C. Cyclosporine 0.5mg/ml (the concentration commercially available in dry eye medication) modestly augmented of the effect of mitomycin C.

Conclusions: : Verapamil and Cyclosporine in clinically acceptable concentrations potentiate the effect of Mitomycin C and may obviate the need for high dose anti-metabolites in trabeculectomy.

Keywords: wound healing • drug toxicity/drug effects 
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