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GFAP-Driven GFP Expression in Activated Mouse Muller Glial Cells Aligning Retinal Blood Vessels Following Intravitreal Injection of AAV2/6 Vectors

Aartsen, WM; van Cleef, KWR; Pellissier, LP; Hoek, RM; Vos, RM; Blits, B; Ehlert, EME; ... Wijnholds, J; + view all (2010) GFAP-Driven GFP Expression in Activated Mouse Muller Glial Cells Aligning Retinal Blood Vessels Following Intravitreal Injection of AAV2/6 Vectors. PLOS ONE , 5 (8) , Article e12387. 10.1371/journal.pone.0012387. Green open access

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Abstract

Background: Muller cell gliosis occurs in various retinal pathologies regardless of the underlying cellular defect. Because activated Muller glial cells span the entire retina and align areas of injury, they are ideal targets for therapeutic strategies, including gene therapy.Methodology/Principal Findings: 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 Muller glial cells aligning the retinal blood vessels. However, the transduction capacity was hindered by the inner limiting membrane (ILM) and besides Muller glial cells, several other inner retinal cell types were transduced. To obtain Muller 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 Muller glial cells aligning retinal blood vessels.Conclusions/Significance: Our experiments indicate that AAV2 vectors carrying the GFAP promoter are a promising tool for specific expression of transgenes in activated glial cells.

Type: Article
Title: GFAP-Driven GFP Expression in Activated Mouse Muller Glial Cells Aligning Retinal Blood Vessels Following Intravitreal Injection of AAV2/6 Vectors
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0012387
Publisher version: http://dx.doi.org/10.1371/journal.pone.0012387
Language: English
Additional information: © 2010 Aartsen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This work was supported in part by Grants from ZonMw [http://www.zonmw.nl/en/organisation/; grant number 43200004 to J.W.], European Commission [HEALTH-F2-2008-200234 to J.W.], Rotterdamse Vereniging Blindenbelangen, Stichting Blindenpenning, Gelderse Blinden Stichting, Stichting Blindenhulp, Landelijke Stichting voor Blinden en Slechtzienden (LSBS) and Algemene Nederlandse Vereniging ter Voorkoming van Blindheid [to W.A. and J.W.]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Keywords: LEBERS CONGENITAL AMAUROSIS, GENE-THERAPY, LENTIVIRAL VECTORS, MAMMALIAN RETINA, TRANSDUCTION, CRB1, DETACHMENT, MEMBRANE, EYE, PHOTORECEPTORS
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
URI: https://discovery.ucl.ac.uk/id/eprint/1311531
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