Korean J Ophthalmol.  2017 Feb;31(1):80-85. 10.3341/kjo.2017.31.1.80.

Effects of Histone Deacetylase Inhibitor (Valproic Acid) on the Expression of Hypoxia-inducible Factor-1 Alpha in Human Retinal Müller Cells

• Kim YJ
• Park SJ
• Kim NR
• Chin HS

• KMID: 2368682
• DOI: http://doi.org/10.3341/kjo.2017.31.1.80

Abstract

PURPOSE
To evaluate the effects of valproic acid (VPA), a histone deacetylase inhibitor (HDACI), on the expression of hypoxia-inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) in human retinal Müller cells under hypoxic conditions.
METHODS
Chemical hypoxia was induced in human retinal Müller cells (MIO-M1) by treatment with increasing concentrations of cobalt(II) chloride (CoCl₂). Müller cells were also treated with a set concentration of CoCl₂, along with various concentrations of VPA. The expression of HIF-1α and VEGF in the treated Müller cells was determined by enzyme-linked immunosorbent assay.
RESULTS
Exposure of human retinal Müller cells to increasing concentrations of CoCl₂ produced a dose-dependent increase in HIF-1α expression. The addition of increasing concentrations of VPA lead to a dose-dependent decrease in expression of HIF-1α and VEGF in Müller cells exposed to a set concentration of CoCl₂.
CONCLUSIONS
HDACI VPA downregulated the expressions of HIF-1α and VEGF in human retinal Müller cells under hypoxic conditions. Using HDACI to target HIF-1α expression in Müller cells could be a new therapeutic strategy for the treatment of retinal vascular diseases.

Keyword

Histone deacetylase inhibitors; Hypoxia-inducible factor 1 alpha; Retinal Muller cells; Valproic acid; Vascular endothelial growth factor

MeSH Terms

Anoxia
Enzyme-Linked Immunosorbent Assay
Ependymoglial Cells
Histone Deacetylase Inhibitors*
Histone Deacetylases*
Histones*
Humans*
Retinaldehyde*
Valproic Acid
Vascular Diseases
Vascular Endothelial Growth Factor A
Histone Deacetylase Inhibitors
Histone Deacetylases
Histones
Retinaldehyde
Valproic Acid
Vascular Endothelial Growth Factor A

Figure

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  Fig. 1 Effects of cobalt(II) chloride (CoCl2) on the expression of hypoxia-inducible factor-1 alpha (HIF-1α) in human retinal Müller cells. *p-value < 0.05.

• 

  Fig. 2 Effects of cobalt(II) chloride (CoCl2) on the survival of human retinal Müller cells. CCK-8 = cell counting kit-8.

• 

  Fig. 3 Effects of increasing concentrations of valproic acid (VPA) on hypoxia-inducible factor-1 alpha (HIF-1α) expression by human retinal Müller cells during hypoxia. *p-value < 0.05.

• 

  Fig. 4 Effects of increasing concentrations of valproic acid (VPA) on vascular endothelial growth factor (VEGF) expression by human retinal Müller cells during hypoxia. *p-value < 0.05.

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