Hydrogen Sulfide Is a Novel Protector of the Retinal Glycocalyx and Endothelial Permeability Barrier
dc.contributor.author | Allen, CL | |
dc.contributor.author | Wolanska, K | |
dc.contributor.author | Malhi, NK | |
dc.contributor.author | Benest, AV | |
dc.contributor.author | Wood, ME | |
dc.contributor.author | Amoaku, W | |
dc.contributor.author | Torregrossa, R | |
dc.contributor.author | Whiteman, M | |
dc.contributor.author | Bates, DO | |
dc.contributor.author | Whatmore, JL | |
dc.date.accessioned | 2021-09-07T10:35:50Z | |
dc.date.issued | 2021-09-07 | |
dc.description.abstract | Significantly reduced levels of the anti-inflammatory gaseous transmitter hydrogen sulfide (H2S) are observed in diabetic patients and correlate with microvascular dysfunction. H2S may protect the microvasculature by preventing loss of the endothelial glycocalyx. We tested the hypothesis that H2S could prevent or treat retinal microvascular endothelial dysfunction in diabetes. Bovine retinal endothelial cells (BRECs) were exposed to normal (NG, 5.5 mmol/L) or high glucose (HG, 25 mmol/L) ± the slow-release H2S donor NaGYY4137 in vitro. Glycocalyx coverage (stained with WGA-FITC) and calcein-labeled monocyte adherence were measured. In vivo, fundus fluorescein angiography (FFA) was performed in normal and streptozotocin-induced (STZ) diabetic rats. Animals received intraocular injection of NaGYY4137 (1 μM) or the mitochondrial-targeted H2S donor AP39 (100 nM) simultaneously with STZ (prevention) or on day 6 after STZ (treatment), and the ratio of interstitial to vascular fluorescence was used to estimate apparent permeability. NaGYY4137 prevented HG-induced loss of BREC glycocalyx, increased monocyte binding to BRECs (p ≤ 0.001), and increased overall glycocalyx coverage (p ≤ 0.001). In rats, the STZ-induced increase in apparent retinal vascular permeability (p ≤ 0.01) was significantly prevented by pre-treatment with NaGYY4137 and AP39 (p < 0.05) and stabilized by their post-STZ administration. NaGYY4137 also reduced the number of acellular capillaries (collagen IV + /IB4-) in the diabetic retina in both groups (p ≤ 0.05). We conclude that NaGYY4137 and AP39 protected the retinal glycocalyx and endothelial permeability barrier from diabetes-associated loss of integrity and reduced the progression of diabetic retinopathy (DR). Hydrogen sulfide donors that target the glycocalyx may therefore be a therapeutic candidate for DR. | en_GB |
dc.description.sponsorship | Medical Research Council (MRC) | en_GB |
dc.description.sponsorship | British Heart Foundation | en_GB |
dc.description.sponsorship | Royal Society | en_GB |
dc.description.sponsorship | Brian Ridge Scholarship | en_GB |
dc.description.sponsorship | National Eye Research Centre | en_GB |
dc.description.sponsorship | Masonic Charitable Foundation | en_GB |
dc.identifier.citation | Vol. 9 | en_GB |
dc.identifier.doi | 10.3389/fcell.2021.724905 | |
dc.identifier.grantnumber | MR/M022706/1 | en_GB |
dc.identifier.grantnumber | MR/L01985X/1 | en_GB |
dc.identifier.grantnumber | PG/18/31/33759 | en_GB |
dc.identifier.grantnumber | RGS\R1\191221 | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/126997 | |
dc.language.iso | en | en_GB |
dc.publisher | Frontiers Media | en_GB |
dc.rights | © 2021 Allen, Wolanska, Malhi, Benest, Wood, Amoaku, Torregrossa, Whiteman, Bates and Whatmore. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. | en_GB |
dc.subject | glycocalyx | en_GB |
dc.subject | retinal permeability | en_GB |
dc.subject | diabetes | en_GB |
dc.subject | hydrogen sulfide | en_GB |
dc.subject | inflammation | en_GB |
dc.subject | mitochondria | en_GB |
dc.subject | slow-release hydrogen sulfide donors | en_GB |
dc.title | Hydrogen Sulfide Is a Novel Protector of the Retinal Glycocalyx and Endothelial Permeability Barrier | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2021-09-07T10:35:50Z | |
dc.description | This is the final version. Available on open access from Frontiers Media via the DOI in this record | en_GB |
dc.description | Data Availability Statement: The original contributions presented in the study are included in the article/supplementary material. The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation. | en_GB |
dc.identifier.eissn | 2296-634X | |
dc.identifier.journal | Frontiers in Cell and Developmental Biology | en_GB |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en_GB |
dcterms.dateAccepted | 2021-07-29 | |
exeter.funder | ::Medical Research Council (MRC) | en_GB |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2021-09-07 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2021-09-07T10:31:03Z | |
refterms.versionFCD | VoR | |
refterms.dateFOA | 2021-09-07T10:36:00Z | |
refterms.panel | A | en_GB |
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Except where otherwise noted, this item's licence is described as © 2021 Allen, Wolanska, Malhi, Benest, Wood, Amoaku, Torregrossa, Whiteman, Bates and Whatmore. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.