Co-treatment of suberoylanilide hydroxamic acid and mitomycin-C induces the apoptosis of rabbit tenon's capsule fibroblast and improves the outcome of glaucoma filtration surgery

Curr Eye Res. 2008 Mar;33(3):237-45. doi: 10.1080/02713680701875281.

Abstract

Purpose: This study was undertaken to develop a new treatment modality that would be able to minimize fibrosis and provide better outcome with glaucoma filtration surgery (GFS).

Methods: We examined whether co-treatment with mitomycin-C (MMC) and histone deacetylase inhibitor (HDACi) suberoylanilide hydroxamic acid (SAHA) efficiently induces apoptosis on rabbit Tenon's capsule fibroblasts (TCF) in vitro. We further examined the effect of co-treatment with SAHA and MMC on the alteration of IOP and the bleb survival in rabbits following GFS.

Results: Co-treatment of MMC and SAHA efficiently induces apoptosis in TCFs via the up-regulation of p53 and increased phosphorylation of p53 on serine 15 and 392. Also, co-treatment of SAHA and low-dose MMC decreases IOP, prolongs bleb survival, and induces apoptosis of cells under the bleb area following GFS.

Conclusion: This study shows that a co-treatment of SAHA and MMC could improve the outcome of GFS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkylating Agents / pharmacology
  • Alkylating Agents / therapeutic use*
  • Animals
  • Apoptosis / drug effects*
  • Blotting, Western
  • Caspase 3 / metabolism
  • Cell Culture Techniques
  • Connective Tissue Cells / drug effects
  • Drug Therapy, Combination
  • Enzyme Inhibitors / pharmacology
  • Enzyme Inhibitors / therapeutic use*
  • Fibroblasts / metabolism
  • Fibroblasts / pathology*
  • Fibrosis / prevention & control
  • Filtering Surgery
  • Fluorescent Antibody Technique, Indirect
  • Glaucoma / surgery*
  • Histone Deacetylase Inhibitors
  • Hydroxamic Acids / pharmacology
  • Hydroxamic Acids / therapeutic use*
  • In Situ Nick-End Labeling
  • Intraocular Pressure / drug effects
  • Mitomycin / pharmacology
  • Mitomycin / therapeutic use*
  • Phosphorylation
  • Rabbits
  • Surgical Flaps
  • Tumor Suppressor Protein p53 / metabolism
  • Up-Regulation
  • Vorinostat
  • bcl-Associated Death Protein / metabolism

Substances

  • Alkylating Agents
  • Enzyme Inhibitors
  • Histone Deacetylase Inhibitors
  • Hydroxamic Acids
  • Tumor Suppressor Protein p53
  • bcl-Associated Death Protein
  • Mitomycin
  • Vorinostat
  • Caspase 3