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Müller Cells Stabilize Microvasculature through Hypoxic Preconditioning

Ou, K; Mertsch, S; Theodoropoulou, S; Wu, J; Liu, J; Copland, DA; Scott, LM; ... Liu, L; + view all (2019) Müller Cells Stabilize Microvasculature through Hypoxic Preconditioning. Cellular Physiology and Biochemistry , 52 (4) pp. 668-680. 10.33594/000000047. Green open access

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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.

Type: Article
Title: Müller Cells Stabilize Microvasculature through Hypoxic Preconditioning
Open access status: An open access version is available from UCL Discovery
DOI: 10.33594/000000047
Publisher version: https://doi.org/10.33594/000000047
Language: English
Additional information: © 2019 The Author(s). Published by Cell Physiol Biochem Press GmbH&Co KG. This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND). Usage and distribution for commercial purposes as well as any distribution of modified material requires written permission.
Keywords: Angiogenesis, Hypoxia, Hypoxic preconditioning, Müller cells, Vascular permeability
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
URI: https://discovery.ucl.ac.uk/id/eprint/10072174
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