Synergistic effects of combined cytotoxic and apoptosis-inducing drugs on Tenon’s capsule fibroblasts in vitro and in vivo

Mietz, Holger; Welsandt, Gerhard; Hueber, Arno; Esser, Carolin

doi:10.1007/s00417-007-0547-z

Cited by 3 publications

(2 citation statements)

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“…A previous study in rabbits also suggested this. 18 In addition, the action of Verapamil on rendering the effect of MMC on HTF cell death relatively dose insensitive, raises the possibility of low dose MMC being applied more precisely during surgery with less potential for complications in adjacent areas. The mechanism through which Verapamil enhances MMC-induced HTF death is unclear, and appears primarily related to enhanced detachment of the cells rather than enhanced MMC-induced HTF apoptosis.…”

Section: Discussionmentioning

confidence: 99%

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P-glycoprotein Blockers Augment the Effect of Mitomycin C on Human Tenon's Fibroblasts

White¹,

Kelly²,

Healey³

et al. 2013

Trans. Vis. Sci. Tech.

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Citation: White AJR, Kelly E, Healey PR, Crowston JG, Mitchell P, Zoellner H. P-glycoprotein blockers augment the effect of Mitomycin C on human Tenon's fibroblasts. Trans Vis Sci Tech. 2013;2(5):1, http:// tvstjournal.org/doi/full/10.1167/tvst. 2.5.1, doi:10.1167/tvst.2.5.1Purpose: Mitomycin C (MMC), which induces apoptosis in human Tenon's fibroblasts (HTF), is frequently used to retard wound healing after glaucoma surgery. The aim of this in vitro study was to examine whether adjunctive Verapamil and Cyclosporine could augment the cytotoxic effect of MMC on HTF.Methods: Fibroblast cell lines were established by explant culture from human tissue biopsy samples obtained during trabeculectomy procedures. Cells were exposed to MMC 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 (2.5-0.25 mg/ml), or Cyclosporine (50-0.5 mg/ml). Following exposure, cells were cultured for 6 hours and surviving cells quantitated by haemocytometer counts.Results: Both Verapamil and Staurosporine exhibited mild toxic effects on their own, but greatly enhanced the apoptotic effect of MMC. Staurosporine is too toxic to be considered clinically, so its augmentive effect on the activity of MMC was not studied further here. Doses as low as 0.25 mg/ml of Verapamil continued to show significant augmentation of the apoptotic effect of MMC Cyclosporine at a clinically used concentration (5 mg/ml) exhibited modest augmentation of the effect of MMC.Conclusions: Verapamil and Cyclosporine in clinically acceptable concentrations potentiate the effect of MMC and may obviate the need for high dose antimetabolites in trabeculectomy; however, further preclinical study is required.Translational Relevance: Adjunctive Verapamil or Cyclosporine may allow lower dose MMC to be used in glaucoma filtration surgery while maintaining the same antifibrotic effects.

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Section: Discussionmentioning

confidence: 99%

“…22 In our experiments, it was difficult to separate the effects of Staurosporine from any truly synergistic activity with MMC. The main reason for inclusion in this study was to confirm a previous in vivo report 18 of the effect of Staurosporine in augmenting the effect of MMC.…”

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confidence: 90%

P-glycoprotein Blockers Augment the Effect of Mitomycin C on Human Tenon's Fibroblasts

White¹,

Kelly²,

Healey³

et al. 2013

Trans. Vis. Sci. Tech.

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Preparation and properties of a drug release membrane of mitomycin C with N-succinyl-hydroxyethyl chitosan

Han

Liu

2011

J Mater Sci: Mater Med

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A novel drug loaded membrane made of N-succinyl-hydroxyethyl chitosan and mitomycin C was used as an implant for glaucoma filtering surgery. The characteristics of the membrane, such as FTIR, equilibrium water content, swelling ratio, permeability, and drug release in vitro were determined. The L929 fibroblast inhibition of drug loaded membranes was compared to hydroxyethyl chitosan film and blank control, detecting by MTT. The biodegradability and biocompatibility were evaluated by implanting membranes into the subcutaneous tissue and muscle of rats. FTIR indicated mitomycin C was introduced. The experimental results indicated the drug loaded membrane was effective on the swelling property, permeability, and drug release in vitro. Cell culture experimental results demonstrated that the destination membrane inhibited fibroblast proliferation. In vivo, the membranes showed bioabsorption and biocompatibility. The experimental results provide a theoretical basis for the future development of the drug loaded membrane as an implant for increasing the success rate of filtering surgery.

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Regulation of Tenon's Capsule Fibroblast Cell Proliferation by the Opioid Growth Factor and the Opioid Growth Factor Receptor Axis

Klocek

Sassani

Donahue³

et al. 2010

Invest. Ophthalmol. Vis. Sci.

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Synergistic effects of combined cytotoxic and apoptosis-inducing drugs on Tenon’s capsule fibroblasts in vitro and in vivo

Cited by 3 publications

References 38 publications

P-glycoprotein Blockers Augment the Effect of Mitomycin C on Human Tenon's Fibroblasts

P-glycoprotein Blockers Augment the Effect of Mitomycin C on Human Tenon's Fibroblasts

Preparation and properties of a drug release membrane of mitomycin C with N-succinyl-hydroxyethyl chitosan

Regulation of Tenon's Capsule Fibroblast Cell Proliferation by the Opioid Growth Factor and the Opioid Growth Factor Receptor Axis

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