May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Regulations of Myofibroblastic Differentiation by Epigenetic Modifications in Corneal Keratocytes
Author Affiliations & Notes
  • Q. Zhou
    Shandong Provincial Key Lab of Ophthalmology, Shandong Eye Institute, Qingdao, China
  • L. Yang
    Shandong Provincial Key Lab of Ophthalmology, Shandong Eye Institute, Qingdao, China
  • Y. Wang
    Shandong Provincial Key Lab of Ophthalmology, Shandong Eye Institute, Qingdao, China
  • P. Chen
    Shandong Provincial Key Lab of Ophthalmology, Shandong Eye Institute, Qingdao, China
  • L. Xie
    Shandong Provincial Key Lab of Ophthalmology, Shandong Eye Institute, Qingdao, China
  • Y. Wang
    Shandong Provincial Key Lab of Ophthalmology, Shandong Eye Institute, Qingdao, China
  • Footnotes
    Commercial Relationships  Q. Zhou, None; L. Yang, None; Y. Wang, None; P. Chen, None; L. Xie, None; Y. Wang, None.
  • Footnotes
    Support  State Key Basic Research (973) Project of China (2007CB516705).
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 4823. doi:https://doi.org/
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      Q. Zhou, L. Yang, Y. Wang, P. Chen, L. Xie, Y. Wang; Regulations of Myofibroblastic Differentiation by Epigenetic Modifications in Corneal Keratocytes. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4823. doi: https://doi.org/.

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

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Abstract

Purpose: : Corneal myofibroblasts differentiated from activated corneal stromal cells are the major producers of extracellular matrix in the process of corneal repairs after injury. Herein the effects of histone deacetylase inhibitors on activation and differentiation of corneal stromal cells were studied.

Methods: : Human and mouse corneal stromal cells (CSCs) were harvested by sequential digestion of corneas by dispase/collagenase and cultured in DMEM/F-12 media under serum-free (quiescent keratocytes) and serum-supplemented (activated corneal fibroblasts) conditions. Myofibroblastic differentiation was induced with TGFβ1 for 5 days in the presence or absence of epigenetic modulators, eg. histone deacetylase inhibitors (HDAC-I, sodium butyrate, trichostatin A), histone methyltransferase inhibitor (HMT-I, 5-aza-2-deoxycytidine). Cell differentiation was monitored by immunocytochemistry, reverse-transcription PCR, and western blot analysis, while proliferation measured by CFSE staining and FACS analysis.

Results: : Treatment of freshly isolated keratocytes with serum or TGFβ induced cell spreading, renewed assembly of actin filaments and expression of α-SMA and collagen I, which was suppressed by the addition of two HDAC-Is, but not the HMT-I. Suppression of myofibroblastic differentiation mediated by HDAC-I was accompanied by reduced cell proliferation. Furthermore, HDAC-I decreased the expression of fibroblast activation protein (FAP) and stromal derived factor-1 (SDF-1), which had been proven to be upregulated during the myofibroblastic differentiation of corneal fibroblasts.

Conclusions: : Inhibition of histone deacetylases suppressed myofibroblastic differentiation and proliferation of corneal fibroblasts, implying that different epigenetic modifications may play important roles in corneal wound healing. Further investigations into the molecular mechanisms may unravel a new scar-prevention strategy.

Keywords: cornea: stroma and keratocytes • differentiation • extracellular matrix 
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