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
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Research Support, Non-U.S. Gov't
MeSH terms
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Alkylating Agents / pharmacology
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Alkylating Agents / therapeutic use*
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Animals
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Apoptosis / drug effects*
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Blotting, Western
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Caspase 3 / metabolism
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Cell Culture Techniques
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Connective Tissue Cells / drug effects
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Drug Therapy, Combination
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Enzyme Inhibitors / pharmacology
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Enzyme Inhibitors / therapeutic use*
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Fibroblasts / metabolism
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Fibroblasts / pathology*
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Fibrosis / prevention & control
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Filtering Surgery
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Fluorescent Antibody Technique, Indirect
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Glaucoma / surgery*
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Histone Deacetylase Inhibitors
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Hydroxamic Acids / pharmacology
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Hydroxamic Acids / therapeutic use*
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In Situ Nick-End Labeling
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Intraocular Pressure / drug effects
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Mitomycin / pharmacology
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Mitomycin / therapeutic use*
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Phosphorylation
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Rabbits
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Surgical Flaps
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Tumor Suppressor Protein p53 / metabolism
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Up-Regulation
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Vorinostat
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bcl-Associated Death Protein / metabolism
Substances
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Alkylating Agents
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Enzyme Inhibitors
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Histone Deacetylase Inhibitors
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Hydroxamic Acids
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Tumor Suppressor Protein p53
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bcl-Associated Death Protein
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Mitomycin
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Vorinostat
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Caspase 3