June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Histone deacetylase inhibitor attenuates TGF-β2 induced human conjunctival fibroblast activation
Author Affiliations & Notes
  • Akiko Futakuchi
    Kumamoto university hospital, Kumamoto city, Japan
  • Toshihiro Inoue
    Kumamoto university hospital, Kumamoto city, Japan
  • Tomokazu Fujimoto
    Kumamoto university hospital, Kumamoto city, Japan
  • Utako Kuroda
    Kumamoto university hospital, Kumamoto city, Japan
  • Miyuki Mochita Inoue
    Kumamoto university hospital, Kumamoto city, Japan
  • Eri Takahashi
    Kumamoto university hospital, Kumamoto city, Japan
  • Kohei Shobayashi
    Kumamoto university hospital, Kumamoto city, Japan
  • Saori Ohira
    Kumamoto university hospital, Kumamoto city, Japan
  • Sachi Kojima
    Kumamoto university hospital, Kumamoto city, Japan
  • Hidenobu Tanihara
    Kumamoto university hospital, Kumamoto city, Japan
  • Footnotes
    Commercial Relationships Akiko Futakuchi, None; Toshihiro Inoue, None; Tomokazu Fujimoto, None; Utako Kuroda, None; Miyuki Inoue, None; Eri Takahashi, None; Kohei Shobayashi, None; Saori Ohira, None; Sachi Kojima, None; Hidenobu Tanihara, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 2678. doi:
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      Akiko Futakuchi, Toshihiro Inoue, Tomokazu Fujimoto, Utako Kuroda, Miyuki Mochita Inoue, Eri Takahashi, Kohei Shobayashi, Saori Ohira, Sachi Kojima, Hidenobu Tanihara; Histone deacetylase inhibitor attenuates TGF-β2 induced human conjunctival fibroblast activation. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2678.

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

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Abstract

Purpose: Excessive scar tissue formation of conjunctiva is a common cause of failure in glaucoma filtration surgery. Fibroblasts can be activated by a variety of inflammatory cytokines and differentiate into myofibroblasts, characterized by aSMA expression and extracellular matrix production, and this activation is known to play a pivotal role in fibrogenesis. Recent studies highlighted the role of antifibrotic activity of histone deacetylase (HDAC) inhibitors. The present study was aimed to evaluate the effects of HDAC inhibitor on TGF-ß2 induced human conjunctival fibroblast activation.

Methods: Human conjunctival fibroblasts were exposed to 5 ng/ml TGF-β2 to induce myofibroblast differentiation. The cultures were pretreated with suberoylanilide hydroxamic acid (SAHA 1.0-5.0 µM) for 1 hour and subsequently incubated with 5 ng/ml TGF-β2 for 48 hours. The effects of SAHA on human conjunctival fibroblasts were analyzed by Western blot analysis and immunocytochemistry. Cell viability and cytotoxicity were assessed using WST-8 assay and Hoechst 33342/propidium iodide (PI) dual staining, respectively.

Results: The expression of a-SMA in TGF-β2 treated human conjunctival fibroblasts was increased in both Western blot analysis (p=0.0009) and immunocytochemistry, and SAHA significantly reduced a-SMA expression (p=0.0011). TGF-β2 increased the proliferation of human conjunctival fibroblasts (p<0.0001), and the effect was significantly attenuated by SAHA (p<0.0001). SAHA did not cause any cellular toxicity at the tested doses.

Conclusions: HDAC inhibitor SAHA attenuated human conjunctival fibroblast differentiation into myofibroblast. Our results suggest that HDAC inhibitors might have a therapeutic potential in the prevention of excess scarring after glaucoma filtration surgery.

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