Ursodeoxycholic Acid Attenuates the Retinal Vascular Abnormalities in Anti-PDGFR-β Antibody-Induced Pericyte Depletion Mouse Models

Abstract As a clinical manifestations of diabetic retinopathy (DR), pericytes (PCs) loss from the capillary walls is thought to be an initial pathological change responsible for the breakdown of the blood-retinal barrier (BRB). This study was performed to investigate the effects of ursodeoxycholic a...

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Autores principales:	Tomoyasu Shiraya, Fumiyuki Araki, Takashi Ueta, Hisako Fukunaga, Kiyohito Totsuka, Takahiro Arai, Akiyoshi Uemura, Kyoji Moriya, Satoshi Kato
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/49dd9235874a46388ff3d093524a0bf7
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spelling	oai:doaj.org-article:49dd9235874a46388ff3d093524a0bf72021-12-02T15:23:47ZUrsodeoxycholic Acid Attenuates the Retinal Vascular Abnormalities in Anti-PDGFR-β Antibody-Induced Pericyte Depletion Mouse Models10.1038/s41598-020-58039-x2045-2322https://doaj.org/article/49dd9235874a46388ff3d093524a0bf72020-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-58039-xhttps://doaj.org/toc/2045-2322Abstract As a clinical manifestations of diabetic retinopathy (DR), pericytes (PCs) loss from the capillary walls is thought to be an initial pathological change responsible for the breakdown of the blood-retinal barrier (BRB). This study was performed to investigate the effects of ursodeoxycholic acid (UDCA) in PC depletion mice by injection of an antibody against platelet-derived growth factor reception-β (PDGFR-β clone APB5). To assess the integrity of the retinal vessels, their density, diameters, vessel branching points, and number of acellular capillaries were evaluated. While all types of retinal vessels became enlarged in APB5-induced mice, treatment with UDCA rescued the vasculature; the vessel density, diameter of the veins and capillaries, and vessel branching points were significantly lower in mice treated with UDCA. Although APB5-induced mice displayed progressive exacerbation of retinal edema, whole retinal thickness upon treatment with UDCA was significantly decreased. Additionally, UDCA reduced the expression of F4/80+ macrophages in the APB5-induced retina according to immunofluorescent labeling. UDCA also reduced the increased expression of angiogenic factors and inflammatory mediators (vascular endothelial growth factor, intercellular adhesion molecule-1, and monocyte chemotactic protein-1). These findings suggest that UDCA can be used to prevent the progression of and treat DR.Tomoyasu ShirayaFumiyuki ArakiTakashi UetaHisako FukunagaKiyohito TotsukaTakahiro AraiAkiyoshi UemuraKyoji MoriyaSatoshi KatoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-8 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tomoyasu Shiraya Fumiyuki Araki Takashi Ueta Hisako Fukunaga Kiyohito Totsuka Takahiro Arai Akiyoshi Uemura Kyoji Moriya Satoshi Kato Ursodeoxycholic Acid Attenuates the Retinal Vascular Abnormalities in Anti-PDGFR-β Antibody-Induced Pericyte Depletion Mouse Models
description	Abstract As a clinical manifestations of diabetic retinopathy (DR), pericytes (PCs) loss from the capillary walls is thought to be an initial pathological change responsible for the breakdown of the blood-retinal barrier (BRB). This study was performed to investigate the effects of ursodeoxycholic acid (UDCA) in PC depletion mice by injection of an antibody against platelet-derived growth factor reception-β (PDGFR-β clone APB5). To assess the integrity of the retinal vessels, their density, diameters, vessel branching points, and number of acellular capillaries were evaluated. While all types of retinal vessels became enlarged in APB5-induced mice, treatment with UDCA rescued the vasculature; the vessel density, diameter of the veins and capillaries, and vessel branching points were significantly lower in mice treated with UDCA. Although APB5-induced mice displayed progressive exacerbation of retinal edema, whole retinal thickness upon treatment with UDCA was significantly decreased. Additionally, UDCA reduced the expression of F4/80+ macrophages in the APB5-induced retina according to immunofluorescent labeling. UDCA also reduced the increased expression of angiogenic factors and inflammatory mediators (vascular endothelial growth factor, intercellular adhesion molecule-1, and monocyte chemotactic protein-1). These findings suggest that UDCA can be used to prevent the progression of and treat DR.
format	article
author	Tomoyasu Shiraya Fumiyuki Araki Takashi Ueta Hisako Fukunaga Kiyohito Totsuka Takahiro Arai Akiyoshi Uemura Kyoji Moriya Satoshi Kato
author_facet	Tomoyasu Shiraya Fumiyuki Araki Takashi Ueta Hisako Fukunaga Kiyohito Totsuka Takahiro Arai Akiyoshi Uemura Kyoji Moriya Satoshi Kato
author_sort	Tomoyasu Shiraya
title	Ursodeoxycholic Acid Attenuates the Retinal Vascular Abnormalities in Anti-PDGFR-β Antibody-Induced Pericyte Depletion Mouse Models
title_short	Ursodeoxycholic Acid Attenuates the Retinal Vascular Abnormalities in Anti-PDGFR-β Antibody-Induced Pericyte Depletion Mouse Models
title_full	Ursodeoxycholic Acid Attenuates the Retinal Vascular Abnormalities in Anti-PDGFR-β Antibody-Induced Pericyte Depletion Mouse Models
title_fullStr	Ursodeoxycholic Acid Attenuates the Retinal Vascular Abnormalities in Anti-PDGFR-β Antibody-Induced Pericyte Depletion Mouse Models
title_full_unstemmed	Ursodeoxycholic Acid Attenuates the Retinal Vascular Abnormalities in Anti-PDGFR-β Antibody-Induced Pericyte Depletion Mouse Models
title_sort	ursodeoxycholic acid attenuates the retinal vascular abnormalities in anti-pdgfr-β antibody-induced pericyte depletion mouse models
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/49dd9235874a46388ff3d093524a0bf7
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Ursodeoxycholic Acid Attenuates the Retinal Vascular Abnormalities in Anti-PDGFR-β Antibody-Induced Pericyte Depletion Mouse Models

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