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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| Format: | Article |
| Language: | English |
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Wiley
2021-01-01
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| Series: | Journal of Ophthalmology |
| Online Access: | http://dx.doi.org/10.1155/2021/5688300 |
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| 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 |
| collection | DOAJ |
| 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 |
| id | doaj-art-be76cb4493744c2dbc2afcd2f45754f6 |
| institution | OA Journals |
| issn | 2090-0058 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Ophthalmology |
| spelling | doaj-art-be76cb4493744c2dbc2afcd2f45754f62025-08-20T02:18:35ZengWileyJournal of Ophthalmology2090-00582021-01-01202110.1155/2021/5688300Effect of Dual Endothelin Receptor Antagonist on a Retinal Degeneration Animal Model by Regulating Choroidal Microvascular MorphologyXiaowei Zhu0Xuming Lin1Ying Xu2Naiyang Li3Qing Zhou4Xiaowei Sun5Yuanbin Li6Department of OphthalmologyDepartment of OphthalmologyGuangdong-Hongkong-Macau Institute of CNS RegenerationDepartment of OphthalmologyDepartment of OphthalmologyDepartment of OphthalmologyDepartment of OphthalmologyObjective. 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.http://dx.doi.org/10.1155/2021/5688300 |
| spellingShingle | 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 Journal of Ophthalmology |
| title | 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_short | 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 |
| url | http://dx.doi.org/10.1155/2021/5688300 |
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