Effect of Dual Endothelin Receptor Antagonist on a Retinal Degeneration Animal Model by Regulating Choroidal Microvascular Morphology

Objective. Clinical studies have found that increasing levels of plasma endothelin-1 (ET-1) might inhibit choroidal blood flow (BF) and promote choroidal vasoconstriction. This study was designed to investigate ET-1 levels and its effect on choroidal microvascular morphology in a retinitis pigmentos...

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Autores principales: Xiaowei Zhu, Xuming Lin, Ying Xu, Naiyang Li, Qing Zhou, Xiaowei Sun, Yuanbin Li
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Publicado: Hindawi Limited 2021
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Acceso en línea:https://doaj.org/article/be76cb4493744c2dbc2afcd2f45754f6
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spelling oai:doaj.org-article:be76cb4493744c2dbc2afcd2f45754f62021-11-29T00:56:25ZEffect of Dual Endothelin Receptor Antagonist on a Retinal Degeneration Animal Model by Regulating Choroidal Microvascular Morphology2090-005810.1155/2021/5688300https://doaj.org/article/be76cb4493744c2dbc2afcd2f45754f62021-01-01T00:00:00Zhttp://dx.doi.org/10.1155/2021/5688300https://doaj.org/toc/2090-0058Objective. Clinical studies have found that increasing levels of plasma endothelin-1 (ET-1) might inhibit choroidal blood flow (BF) and promote choroidal vasoconstriction. This study was designed to investigate ET-1 levels and its effect on choroidal microvascular morphology in a retinitis pigmentosa (RP) animal model. Methods. Mice with retinal degeneration (rd10) were intragastrically administered bosentan, a dual endothelin receptor antagonist. We detected plasma ET-1 levels using an enzyme-linked immunosorbent assay (ELISA) kit at P14, P21, and P28 and evaluated ET-1 expression in RPE/choroid/sclera complexes using western blot and whole mount immunofluorescence staining at P28. Retinal thickness was measured using hematoxylin and eosin (H&E) staining at P28. At the same time, we also estimated choroidal microvascular densities using vascular luminal casting with a scanning electron microscope (SEM). Results. Plasma ET-1 levels were increased significantly in rd10 mice at P21 (65.48 ± 24.83 pg/ml) and P28 (85.89 ± 20.23 pg/ml) compared with C57BL/6J mice at P21 (33.52 ± 16.33 pg/ml) and P28 (42.38 ± 17.53 pg/ml); the expression of ET-1 was also upregulated in RPE/choroid/sclera complexes at P28. Bosentan inhibited ET-1 expression in plasma (P<0.05) and RPE/choroid/sclera complexes at P28 in rd10 mice. Choroidal microvascular densities were decreased in rd10 mice, and bosentan could weaken these changes. Conclusion. Plasma and local ET-1 was elevated in an animal model of RP, suggesting that it likely participates in the pathological progression of retinal degeneration and may thus provide a new intervention target. ET-1 blockade might exert its protective effect by elevating choroidal microvascular density via inhibition of ET-1.Xiaowei ZhuXuming LinYing XuNaiyang LiQing ZhouXiaowei SunYuanbin LiHindawi LimitedarticleOphthalmologyRE1-994ENJournal of Ophthalmology, Vol 2021 (2021)
institution DOAJ
collection DOAJ
language EN
topic Ophthalmology
RE1-994
spellingShingle Ophthalmology
RE1-994
Xiaowei Zhu
Xuming Lin
Ying Xu
Naiyang Li
Qing Zhou
Xiaowei Sun
Yuanbin Li
Effect of Dual Endothelin Receptor Antagonist on a Retinal Degeneration Animal Model by Regulating Choroidal Microvascular Morphology
description Objective. Clinical studies have found that increasing levels of plasma endothelin-1 (ET-1) might inhibit choroidal blood flow (BF) and promote choroidal vasoconstriction. This study was designed to investigate ET-1 levels and its effect on choroidal microvascular morphology in a retinitis pigmentosa (RP) animal model. Methods. Mice with retinal degeneration (rd10) were intragastrically administered bosentan, a dual endothelin receptor antagonist. We detected plasma ET-1 levels using an enzyme-linked immunosorbent assay (ELISA) kit at P14, P21, and P28 and evaluated ET-1 expression in RPE/choroid/sclera complexes using western blot and whole mount immunofluorescence staining at P28. Retinal thickness was measured using hematoxylin and eosin (H&E) staining at P28. At the same time, we also estimated choroidal microvascular densities using vascular luminal casting with a scanning electron microscope (SEM). Results. Plasma ET-1 levels were increased significantly in rd10 mice at P21 (65.48 ± 24.83 pg/ml) and P28 (85.89 ± 20.23 pg/ml) compared with C57BL/6J mice at P21 (33.52 ± 16.33 pg/ml) and P28 (42.38 ± 17.53 pg/ml); the expression of ET-1 was also upregulated in RPE/choroid/sclera complexes at P28. Bosentan inhibited ET-1 expression in plasma (P<0.05) and RPE/choroid/sclera complexes at P28 in rd10 mice. Choroidal microvascular densities were decreased in rd10 mice, and bosentan could weaken these changes. Conclusion. Plasma and local ET-1 was elevated in an animal model of RP, suggesting that it likely participates in the pathological progression of retinal degeneration and may thus provide a new intervention target. ET-1 blockade might exert its protective effect by elevating choroidal microvascular density via inhibition of ET-1.
format article
author Xiaowei Zhu
Xuming Lin
Ying Xu
Naiyang Li
Qing Zhou
Xiaowei Sun
Yuanbin Li
author_facet Xiaowei Zhu
Xuming Lin
Ying Xu
Naiyang Li
Qing Zhou
Xiaowei Sun
Yuanbin Li
author_sort Xiaowei Zhu
title Effect of Dual Endothelin Receptor Antagonist on a Retinal Degeneration Animal Model by Regulating Choroidal Microvascular Morphology
title_short Effect of Dual Endothelin Receptor Antagonist on a Retinal Degeneration Animal Model by Regulating Choroidal Microvascular Morphology
title_full Effect of Dual Endothelin Receptor Antagonist on a Retinal Degeneration Animal Model by Regulating Choroidal Microvascular Morphology
title_fullStr Effect of Dual Endothelin Receptor Antagonist on a Retinal Degeneration Animal Model by Regulating Choroidal Microvascular Morphology
title_full_unstemmed Effect of Dual Endothelin Receptor Antagonist on a Retinal Degeneration Animal Model by Regulating Choroidal Microvascular Morphology
title_sort effect of dual endothelin receptor antagonist on a retinal degeneration animal model by regulating choroidal microvascular morphology
publisher Hindawi Limited
publishDate 2021
url https://doaj.org/article/be76cb4493744c2dbc2afcd2f45754f6
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AT yingxu effectofdualendothelinreceptorantagonistonaretinaldegenerationanimalmodelbyregulatingchoroidalmicrovascularmorphology
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AT xiaoweisun effectofdualendothelinreceptorantagonistonaretinaldegenerationanimalmodelbyregulatingchoroidalmicrovascularmorphology
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