Effects of Resveratrol on Vascular Function in Retinal Ischemia-Reperfusion Injury

Ischemia-reperfusion (I/R) events are involved in the development of various ocular pathologies, e.g., retinal artery or vein occlusion. We tested the hypothesis that resveratrol is protective against I/R injury in the murine retina. Intraocular pressure (IOP) was elevated in anaesthetized mice to 1...

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Main Authors: Panagiotis Chronopoulos, Caroline Manicam, Jenia Kouchek Zadeh, Panagiotis Laspas, Johanna Charlotte Unkrig, Marie Luise Göbel, Aytan Musayeva, Norbert Pfeiffer, Matthias Oelze, Andreas Daiber, Huige Li, Ning Xia, Adrian Gericke
Format: Article
Language:English
Published: MDPI AG 2023-04-01
Series:Antioxidants
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Online Access:https://www.mdpi.com/2076-3921/12/4/853
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author Panagiotis Chronopoulos
Caroline Manicam
Jenia Kouchek Zadeh
Panagiotis Laspas
Johanna Charlotte Unkrig
Marie Luise Göbel
Aytan Musayeva
Norbert Pfeiffer
Matthias Oelze
Andreas Daiber
Huige Li
Ning Xia
Adrian Gericke
author_facet Panagiotis Chronopoulos
Caroline Manicam
Jenia Kouchek Zadeh
Panagiotis Laspas
Johanna Charlotte Unkrig
Marie Luise Göbel
Aytan Musayeva
Norbert Pfeiffer
Matthias Oelze
Andreas Daiber
Huige Li
Ning Xia
Adrian Gericke
author_sort Panagiotis Chronopoulos
collection DOAJ
description Ischemia-reperfusion (I/R) events are involved in the development of various ocular pathologies, e.g., retinal artery or vein occlusion. We tested the hypothesis that resveratrol is protective against I/R injury in the murine retina. Intraocular pressure (IOP) was elevated in anaesthetized mice to 110 mm Hg for 45 min via a micropipette placed in the anterior chamber to induce ocular ischemia. In the fellow eye, which served as control, IOP was kept at a physiological level. One group received resveratrol (30 mg/kg/day p.o. once daily) starting one day before the I/R event, whereas the other group of mice received vehicle solution only. On day eight after the I/R event, mice were sacrificed and retinal wholemounts were prepared and immuno-stained using a Brn3a antibody to quantify retinal ganglion cells. Reactivity of retinal arterioles was measured in retinal vascular preparations using video microscopy. Reactive oxygen species (ROS) and nitrogen species (RNS) were quantified in ocular cryosections by dihydroethidium and anti-3-nitrotyrosine staining, respectively. Moreover, hypoxic, redox and nitric oxide synthase gene expression was quantified in retinal explants by PCR. I/R significantly diminished retinal ganglion cell number in vehicle-treated mice. Conversely, only a negligible reduction in retinal ganglion cell number was observed in resveratrol-treated mice following I/R. Endothelial function and autoregulation were markedly reduced, which was accompanied by increased ROS and RNS in retinal blood vessels of vehicle-exposed mice following I/R, whereas resveratrol preserved vascular endothelial function and autoregulation and blunted ROS and RNS formation. Moreover, resveratrol reduced I/R-induced mRNA expression for the prooxidant enzyme, nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2). Our data provide evidence that resveratrol protects from I/R-induced retinal ganglion cell loss and endothelial dysfunction in the murine retina by reducing nitro-oxidative stress possibly via suppression of NOX2 upregulation.
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spelling doaj.art-12abbd60732d43ba83a355cc31a186d32023-11-17T18:05:14ZengMDPI AGAntioxidants2076-39212023-04-0112485310.3390/antiox12040853Effects of Resveratrol on Vascular Function in Retinal Ischemia-Reperfusion InjuryPanagiotis Chronopoulos0Caroline Manicam1Jenia Kouchek Zadeh2Panagiotis Laspas3Johanna Charlotte Unkrig4Marie Luise Göbel5Aytan Musayeva6Norbert Pfeiffer7Matthias Oelze8Andreas Daiber9Huige Li10Ning Xia11Adrian Gericke12Department of Ophthalmology, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, GermanyDepartment of Ophthalmology, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, GermanyDepartment of Ophthalmology, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, GermanyDepartment of Ophthalmology, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, GermanyDepartment of Ophthalmology, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, GermanyDepartment of Ophthalmology, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, GermanyDepartment of Ophthalmology, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, GermanyDepartment of Ophthalmology, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, GermanyDepartment of Cardiology, Cardiology 1, University Medical Center, Johannes Gutenberg University, Langenbeckstrasse 1, 55131 Mainz, GermanyDepartment of Cardiology, Cardiology 1, University Medical Center, Johannes Gutenberg University, Langenbeckstrasse 1, 55131 Mainz, GermanyDepartment of Pharmacology, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, GermanyDepartment of Pharmacology, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, GermanyDepartment of Ophthalmology, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, GermanyIschemia-reperfusion (I/R) events are involved in the development of various ocular pathologies, e.g., retinal artery or vein occlusion. We tested the hypothesis that resveratrol is protective against I/R injury in the murine retina. Intraocular pressure (IOP) was elevated in anaesthetized mice to 110 mm Hg for 45 min via a micropipette placed in the anterior chamber to induce ocular ischemia. In the fellow eye, which served as control, IOP was kept at a physiological level. One group received resveratrol (30 mg/kg/day p.o. once daily) starting one day before the I/R event, whereas the other group of mice received vehicle solution only. On day eight after the I/R event, mice were sacrificed and retinal wholemounts were prepared and immuno-stained using a Brn3a antibody to quantify retinal ganglion cells. Reactivity of retinal arterioles was measured in retinal vascular preparations using video microscopy. Reactive oxygen species (ROS) and nitrogen species (RNS) were quantified in ocular cryosections by dihydroethidium and anti-3-nitrotyrosine staining, respectively. Moreover, hypoxic, redox and nitric oxide synthase gene expression was quantified in retinal explants by PCR. I/R significantly diminished retinal ganglion cell number in vehicle-treated mice. Conversely, only a negligible reduction in retinal ganglion cell number was observed in resveratrol-treated mice following I/R. Endothelial function and autoregulation were markedly reduced, which was accompanied by increased ROS and RNS in retinal blood vessels of vehicle-exposed mice following I/R, whereas resveratrol preserved vascular endothelial function and autoregulation and blunted ROS and RNS formation. Moreover, resveratrol reduced I/R-induced mRNA expression for the prooxidant enzyme, nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2). Our data provide evidence that resveratrol protects from I/R-induced retinal ganglion cell loss and endothelial dysfunction in the murine retina by reducing nitro-oxidative stress possibly via suppression of NOX2 upregulation.https://www.mdpi.com/2076-3921/12/4/853arteriolesischemia-reperfusion injuryreactive oxygen speciesresveratrolretina
spellingShingle Panagiotis Chronopoulos
Caroline Manicam
Jenia Kouchek Zadeh
Panagiotis Laspas
Johanna Charlotte Unkrig
Marie Luise Göbel
Aytan Musayeva
Norbert Pfeiffer
Matthias Oelze
Andreas Daiber
Huige Li
Ning Xia
Adrian Gericke
Effects of Resveratrol on Vascular Function in Retinal Ischemia-Reperfusion Injury
Antioxidants
arterioles
ischemia-reperfusion injury
reactive oxygen species
resveratrol
retina
title Effects of Resveratrol on Vascular Function in Retinal Ischemia-Reperfusion Injury
title_full Effects of Resveratrol on Vascular Function in Retinal Ischemia-Reperfusion Injury
title_fullStr Effects of Resveratrol on Vascular Function in Retinal Ischemia-Reperfusion Injury
title_full_unstemmed Effects of Resveratrol on Vascular Function in Retinal Ischemia-Reperfusion Injury
title_short Effects of Resveratrol on Vascular Function in Retinal Ischemia-Reperfusion Injury
title_sort effects of resveratrol on vascular function in retinal ischemia reperfusion injury
topic arterioles
ischemia-reperfusion injury
reactive oxygen species
resveratrol
retina
url https://www.mdpi.com/2076-3921/12/4/853
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