Deletion of TSPO Causes Dysregulation of Cholesterol Metabolism in Mouse Retina

Cholesterol dysregulation has been implicated in age-related macular degeneration (AMD), the most common cause of visual impairment in the elderly. The 18 KDa translocator protein (TSPO) is a mitochondrial outer membrane protein responsible for transporting cholesterol from the mitochondrial outer m...

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Autores principales:	Fahad Farhan, Mohammad Almarhoun, Aileen Wong, Amy S. Findlay, Chris Bartholomew, Mark T. S. Williams, Toby W. Hurd, Xinhua Shu
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	TSPO retina cholesterol inflammation age-related macular degeneration Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/4317af5552b84e9aab650b9822531d40
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spelling	oai:doaj.org-article:4317af5552b84e9aab650b9822531d402021-11-25T17:11:04ZDeletion of TSPO Causes Dysregulation of Cholesterol Metabolism in Mouse Retina10.3390/cells101130662073-4409https://doaj.org/article/4317af5552b84e9aab650b9822531d402021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3066https://doaj.org/toc/2073-4409Cholesterol dysregulation has been implicated in age-related macular degeneration (AMD), the most common cause of visual impairment in the elderly. The 18 KDa translocator protein (TSPO) is a mitochondrial outer membrane protein responsible for transporting cholesterol from the mitochondrial outer membrane to the inner membrane. TSPO is highly expressed in retinal pigment epithelial (RPE) cells, and TSPO ligands have shown therapeutic potential for the treatment of AMD. Here, we characterized retinal pathology of <i>Tspo</i> knockout (KO) mice using histological, immunohistochemical, biochemical and molecular biological approaches. We found that <i>Tspo</i> KO mice had normal retinal morphology (by light microscopy) but showed elevated levels of cholesterol, triglycerides and phospholipids with perturbed cholesterol efflux in the RPE cells of <i>Tspo</i> KO mice. Expression of cholesterol-associated genes (<i>Nr1h3</i>, <i>Abca1</i>, <i>Abcg1</i>, <i>Cyp27a1</i> and <i>Cyp46a1</i>) was significantly downregulated, and production of pro-inflammatory cytokines was markedly increased in <i>Tspo</i> KO retinas. Furthermore, microglial activation was also observed in <i>Tspo</i> KO mouse retinas. These findings provide new insights into the function of TSPO in the retina and may aid in the design of new therapeutic strategies for the treatment of AMD.Fahad FarhanMohammad AlmarhounAileen WongAmy S. FindlayChris BartholomewMark T. S. WilliamsToby W. HurdXinhua ShuMDPI AGarticleTSPOretinacholesterolinflammationage-related macular degenerationBiology (General)QH301-705.5ENCells, Vol 10, Iss 3066, p 3066 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	TSPO retina cholesterol inflammation age-related macular degeneration Biology (General) QH301-705.5
spellingShingle	TSPO retina cholesterol inflammation age-related macular degeneration Biology (General) QH301-705.5 Fahad Farhan Mohammad Almarhoun Aileen Wong Amy S. Findlay Chris Bartholomew Mark T. S. Williams Toby W. Hurd Xinhua Shu Deletion of TSPO Causes Dysregulation of Cholesterol Metabolism in Mouse Retina
description	Cholesterol dysregulation has been implicated in age-related macular degeneration (AMD), the most common cause of visual impairment in the elderly. The 18 KDa translocator protein (TSPO) is a mitochondrial outer membrane protein responsible for transporting cholesterol from the mitochondrial outer membrane to the inner membrane. TSPO is highly expressed in retinal pigment epithelial (RPE) cells, and TSPO ligands have shown therapeutic potential for the treatment of AMD. Here, we characterized retinal pathology of <i>Tspo</i> knockout (KO) mice using histological, immunohistochemical, biochemical and molecular biological approaches. We found that <i>Tspo</i> KO mice had normal retinal morphology (by light microscopy) but showed elevated levels of cholesterol, triglycerides and phospholipids with perturbed cholesterol efflux in the RPE cells of <i>Tspo</i> KO mice. Expression of cholesterol-associated genes (<i>Nr1h3</i>, <i>Abca1</i>, <i>Abcg1</i>, <i>Cyp27a1</i> and <i>Cyp46a1</i>) was significantly downregulated, and production of pro-inflammatory cytokines was markedly increased in <i>Tspo</i> KO retinas. Furthermore, microglial activation was also observed in <i>Tspo</i> KO mouse retinas. These findings provide new insights into the function of TSPO in the retina and may aid in the design of new therapeutic strategies for the treatment of AMD.
format	article
author	Fahad Farhan Mohammad Almarhoun Aileen Wong Amy S. Findlay Chris Bartholomew Mark T. S. Williams Toby W. Hurd Xinhua Shu
author_facet	Fahad Farhan Mohammad Almarhoun Aileen Wong Amy S. Findlay Chris Bartholomew Mark T. S. Williams Toby W. Hurd Xinhua Shu
author_sort	Fahad Farhan
title	Deletion of TSPO Causes Dysregulation of Cholesterol Metabolism in Mouse Retina
title_short	Deletion of TSPO Causes Dysregulation of Cholesterol Metabolism in Mouse Retina
title_full	Deletion of TSPO Causes Dysregulation of Cholesterol Metabolism in Mouse Retina
title_fullStr	Deletion of TSPO Causes Dysregulation of Cholesterol Metabolism in Mouse Retina
title_full_unstemmed	Deletion of TSPO Causes Dysregulation of Cholesterol Metabolism in Mouse Retina
title_sort	deletion of tspo causes dysregulation of cholesterol metabolism in mouse retina
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/4317af5552b84e9aab650b9822531d40
work_keys_str_mv	AT fahadfarhan deletionoftspocausesdysregulationofcholesterolmetabolisminmouseretina AT mohammadalmarhoun deletionoftspocausesdysregulationofcholesterolmetabolisminmouseretina AT aileenwong deletionoftspocausesdysregulationofcholesterolmetabolisminmouseretina AT amysfindlay deletionoftspocausesdysregulationofcholesterolmetabolisminmouseretina AT chrisbartholomew deletionoftspocausesdysregulationofcholesterolmetabolisminmouseretina AT marktswilliams deletionoftspocausesdysregulationofcholesterolmetabolisminmouseretina AT tobywhurd deletionoftspocausesdysregulationofcholesterolmetabolisminmouseretina AT xinhuashu deletionoftspocausesdysregulationofcholesterolmetabolisminmouseretina
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Deletion of TSPO Causes Dysregulation of Cholesterol Metabolism in Mouse Retina

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