Retinal hypoxia induces vascular endothelial growth factor through induction of estrogen-related receptor γ

Biochemical and Biophysical Research Communications
Ji Yeon DoDong Ho Park

Abstract

Ischemic retinopathies causing overexpression of pro-angiogenic factors, including vascular endothelial growth factor (VEGF), are the most common cause of blindness. Thus, understanding the pathophysiology of targetable pathways that regulate retinal VEGF is of great interest. A conserved binding site for estrogen-related receptor γ (ERRγ) has been identified in the promoter of the Vegfa gene. ERRγ is a constitutively active orphan nuclear receptor and its expression is increased by hypoxic stimuli in metabolically active tissues. This study evaluated the role of ERRγ in the ischemic retina and the anti-VEGF potential of GSK5182, a selective inverse agonist of ERRγ. In an oxygen-induced retinopathy (OIR) mouse model, immunohistochemistry showed significantly increased ERRγ expression in the ganglion cell layer at postnatal day (P) 17. In a ganglion cell line (RGC-5), mRNA and protein levels of ERRγ were increased by desferrioxamine treatment and hypoxic conditions (1% O2). Transient transfection of RGC-5 cells revealed that ERRγ regulated Vegfa expression and this was inhibited by GSK5182. Intravitreal injection of GSK5182 into the OIR model at P14 inhibited retinal Vegfa mRNA expression at P17. GSK5182 suppresses hypoxia-induc...Continue Reading

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Citations

Feb 18, 2016·Oxidative Medicine and Cellular Longevity·María Luisa Fanjul-Moles, Germán Octavio López-Riquelme
Jan 4, 2017·Journal of Diabetes·Yi Shi, Paul M Vanhoutte
Sep 26, 2015·Arteriosclerosis, Thrombosis, and Vascular Biology·Ji-Hyun KimIn-Kyu Lee
Oct 4, 2019·Environmental Science and Pollution Research International·Mehmet AtesNazan Uysal

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