Interferon-alpha and interferon-gamma modulate Fas-mediated apoptosis in mitomycin-C-resistant human Tenon's

Xiao Yang Wang1, Jonathan G Crowston, Andrew J R White

  • 1Centre for Vision Research, Westmead Millennium Institute, The University of Sydney, Sydney, New South Wales, Australia.

Abstract

Insights

Interferon-alpha and gamma restore sensitivity to Fas-mediated apoptosis in mitomycin-C-resistant cells. This offers a potential alternative anti-fibrotic strategy for trabeculectomy surgery.

Area of Science:

  • Ophthalmology
  • Cell Biology
  • Pharmacology

Background:

  • Trabeculectomy is a surgical procedure to treat glaucoma.
  • Mitomycin-C is commonly used to prevent fibrosis after trabeculectomy, but resistance can develop.
  • Investigating alternative anti-fibrotic agents is crucial for improving surgical outcomes.

Purpose of the Study:

  • To evaluate interferon-alpha and interferon-gamma as potential anti-fibrotic agents.
  • To determine if these interferons can sensitize mitomycin-C-resistant Tenon's fibroblasts to Fas-mediated apoptosis.
  • To explore their use as an alternative to mitomycin-C in trabeculectomy.

Main Methods:

  • Utilized a mitomycin-C-resistant human Tenon's fibroblast cell line.
  • Pretreated cells with interferon-alpha and/or interferon-gamma.
  • Stimulated cells with an agonistic Fas antibody to induce cell death.
  • Analyzed apoptosis-related protein expression via flow cytometry and Western blot.

Main Results:

  • Interferon-alpha and gamma upregulated Fas, Fas-associated protein with death domain, and caspase-8 expression.
  • Combined interferon treatment synergistically increased cell death sensitivity.
  • Fas-mediated apoptosis was confirmed by blocking effects with an anti-Fas antibody and caspase inhibitors.

Conclusions:

  • Interferon-alpha and interferon-gamma can re-sensitize mitomycin-C-resistant cells to Fas-mediated apoptosis.
  • This mechanism involves enhanced death-inducing signaling complex formation.
  • These findings suggest a novel anti-fibrotic strategy for trabeculectomy.

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