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Müller Cells Stabilize Microvasculature through Hypoxic Preconditioning.

Research output: Contribution to journalArticle

Original languageEnglish
Pages (from-to)668-680
Number of pages13
JournalCellular Physiology and Biochemistry
Volume52
DOIs
DateAccepted/In press - 25 Mar 2019

Abstract

BACKGROUND/AIMS:
Hypoxia of the retina is a common pathogenic drive leading to vision loss as a result of tissue ischemia, increased vascular permeability and ultimately retinal neovascularisation. Here we tested the hypothesis that Müller cells stabilize the neurovascular unit, microvasculature by suppression of HIF-1α activation as a result of hypoxic preconditioning.

METHODS:
Tube Formation Assay and In vitro Vascular Permeability Image Assay were used to analyze angiogenesis and vascular integrity. Seahorse XF Cell Mito Stress Test was used to measure mitochondrial respiration. Gene and protein expression were examined by qRTPCR, ELISA and western blot.

RESULTS:
Hypoxic insult induces a significant induction of proangiogenic factors including vascular endothelial growth factor (VEGF) and angiopoietinlike 4 (ANGPTL-4) resulting in angiogenesis and increased vascular permeability of vascular endothelial cells. Hypoxic preconditioning of a human retinal Müller glia cell line significantly attenuates HIF-1α activation through the inhibition of mTOR and concomitant induction of aerobic glycolysis, stabilizing endothelial cells.

CONCLUSION:
Hypoxic preconditioning of Müller cells confers a robust protection to endothelial cells, through the suppression of HIF1α activation and its downstream regulation of VEGF and ANGPTL-4.

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    Rights statement: This is the final published version of the article (version of record). It first appeared online via Cell Physiol Biochem Press at https://doi.org/10.33594/000000047 . Please refer to any applicable terms of use of the publisher.

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