GFAP-driven GFP expression in activated mouse Müller glial cells aligning retinal blood vessels following intravitreal injection of AAV2/6 vectors.

<h4>Background</h4>Müller cell gliosis occurs in various retinal pathologies regardless of the underlying cellular defect. Because activated Müller glial cells span the entire retina and align areas of injury, they are ideal targets for therapeutic strategies, including gene therapy.<...

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Autores principales:	Wendy M Aartsen, Koen W R van Cleef, Lucie P Pellissier, Robert M Hoek, Rogier M Vos, Bas Blits, Erich M E Ehlert, Kamaljit S Balaggan, Robin R Ali, Joost Verhaagen, Jan Wijnholds
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fbe4eb2ddd3748f092d1484bcd58d2f2
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spelling	oai:doaj.org-article:fbe4eb2ddd3748f092d1484bcd58d2f22021-11-18T06:35:46ZGFAP-driven GFP expression in activated mouse Müller glial cells aligning retinal blood vessels following intravitreal injection of AAV2/6 vectors.1932-620310.1371/journal.pone.0012387https://doaj.org/article/fbe4eb2ddd3748f092d1484bcd58d2f22010-08-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20808778/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Müller cell gliosis occurs in various retinal pathologies regardless of the underlying cellular defect. Because activated Müller glial cells span the entire retina and align areas of injury, they are ideal targets for therapeutic strategies, including gene therapy.<h4>Methodology/principal findings</h4>We used adeno-associated viral AAV2/6 vectors to transduce mouse retinas. The transduction pattern of AAV2/6 was investigated by studying expression of the green fluorescent protein (GFP) transgene using scanning-laser ophthalmoscopy and immuno-histochemistry. AAV2/6 vectors transduced mouse Müller glial cells aligning the retinal blood vessels. However, the transduction capacity was hindered by the inner limiting membrane (ILM) and besides Müller glial cells, several other inner retinal cell types were transduced. To obtain Müller glial cell-specific transgene expression, the cytomegalovirus (CMV) promoter was replaced by the glial fibrillary acidic protein (GFAP) promoter. Specificity and activation of the GFAP promoter was tested in a mouse model for retinal gliosis. Mice deficient for Crumbs homologue 1 (CRB1) develop gliosis after light exposure. Light exposure of Crb1(-/-) retinas transduced with AAV2/6-GFAP-GFP induced GFP expression restricted to activated Müller glial cells aligning retinal blood vessels.<h4>Conclusions/significance</h4>Our experiments indicate that AAV2 vectors carrying the GFAP promoter are a promising tool for specific expression of transgenes in activated glial cells.Wendy M AartsenKoen W R van CleefLucie P PellissierRobert M HoekRogier M VosBas BlitsErich M E EhlertKamaljit S BalagganRobin R AliJoost VerhaagenJan WijnholdsPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 8, p e12387 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Wendy M Aartsen Koen W R van Cleef Lucie P Pellissier Robert M Hoek Rogier M Vos Bas Blits Erich M E Ehlert Kamaljit S Balaggan Robin R Ali Joost Verhaagen Jan Wijnholds GFAP-driven GFP expression in activated mouse Müller glial cells aligning retinal blood vessels following intravitreal injection of AAV2/6 vectors.
description	<h4>Background</h4>Müller cell gliosis occurs in various retinal pathologies regardless of the underlying cellular defect. Because activated Müller glial cells span the entire retina and align areas of injury, they are ideal targets for therapeutic strategies, including gene therapy.<h4>Methodology/principal findings</h4>We used adeno-associated viral AAV2/6 vectors to transduce mouse retinas. The transduction pattern of AAV2/6 was investigated by studying expression of the green fluorescent protein (GFP) transgene using scanning-laser ophthalmoscopy and immuno-histochemistry. AAV2/6 vectors transduced mouse Müller glial cells aligning the retinal blood vessels. However, the transduction capacity was hindered by the inner limiting membrane (ILM) and besides Müller glial cells, several other inner retinal cell types were transduced. To obtain Müller glial cell-specific transgene expression, the cytomegalovirus (CMV) promoter was replaced by the glial fibrillary acidic protein (GFAP) promoter. Specificity and activation of the GFAP promoter was tested in a mouse model for retinal gliosis. Mice deficient for Crumbs homologue 1 (CRB1) develop gliosis after light exposure. Light exposure of Crb1(-/-) retinas transduced with AAV2/6-GFAP-GFP induced GFP expression restricted to activated Müller glial cells aligning retinal blood vessels.<h4>Conclusions/significance</h4>Our experiments indicate that AAV2 vectors carrying the GFAP promoter are a promising tool for specific expression of transgenes in activated glial cells.
format	article
author	Wendy M Aartsen Koen W R van Cleef Lucie P Pellissier Robert M Hoek Rogier M Vos Bas Blits Erich M E Ehlert Kamaljit S Balaggan Robin R Ali Joost Verhaagen Jan Wijnholds
author_facet	Wendy M Aartsen Koen W R van Cleef Lucie P Pellissier Robert M Hoek Rogier M Vos Bas Blits Erich M E Ehlert Kamaljit S Balaggan Robin R Ali Joost Verhaagen Jan Wijnholds
author_sort	Wendy M Aartsen
title	GFAP-driven GFP expression in activated mouse Müller glial cells aligning retinal blood vessels following intravitreal injection of AAV2/6 vectors.
title_short	GFAP-driven GFP expression in activated mouse Müller glial cells aligning retinal blood vessels following intravitreal injection of AAV2/6 vectors.
title_full	GFAP-driven GFP expression in activated mouse Müller glial cells aligning retinal blood vessels following intravitreal injection of AAV2/6 vectors.
title_fullStr	GFAP-driven GFP expression in activated mouse Müller glial cells aligning retinal blood vessels following intravitreal injection of AAV2/6 vectors.
title_full_unstemmed	GFAP-driven GFP expression in activated mouse Müller glial cells aligning retinal blood vessels following intravitreal injection of AAV2/6 vectors.
title_sort	gfap-driven gfp expression in activated mouse müller glial cells aligning retinal blood vessels following intravitreal injection of aav2/6 vectors.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/fbe4eb2ddd3748f092d1484bcd58d2f2
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GFAP-driven GFP expression in activated mouse Müller glial cells aligning retinal blood vessels following intravitreal injection of AAV2/6 vectors.

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