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Trans-Ocular Electric Current In Vivo Enhances AAV-Mediated Retinal Transduction in Large Animal Eye After Intravitreal Vector Administration.
Song, Hongman; Zeng, Yong; Sardar Pasha, Sheik Pran Babu; Bush, Ronald A; Vijayasarathy, Camasamudram; Qian, Haohua; Wei, Lisa; Wiley, Henry E; Wu, Zhijian; Sieving, Paul A.
Afiliación
  • Song H; Section for Translational Research on Retinal and Macular Degeneration, National Institute on Deafness and Other Communication Disorders, Bethesda, MD, USA.
  • Zeng Y; National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
  • Sardar Pasha SPB; Section for Translational Research on Retinal and Macular Degeneration, National Institute on Deafness and Other Communication Disorders, Bethesda, MD, USA.
  • Bush RA; National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
  • Vijayasarathy C; Department of Ophthalmology, School of Medicine, University of California at Davis, Sacramento, CA, USA.
  • Qian H; Section for Translational Research on Retinal and Macular Degeneration, National Institute on Deafness and Other Communication Disorders, Bethesda, MD, USA.
  • Wei L; National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
  • Wiley HE; Section for Translational Research on Retinal and Macular Degeneration, National Institute on Deafness and Other Communication Disorders, Bethesda, MD, USA.
  • Wu Z; National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
  • Sieving PA; National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
Transl Vis Sci Technol ; 9(7): 28, 2020 06.
Article en En | MEDLINE | ID: mdl-32844051
Purpose: Electric micro-current has been shown to enhance penetration and transduction of adeno-associated viral (AAV) vectors in mouse retina after intravitreal administration. We termed this: "electric-current vector mobility (ECVM)." The present study considered whether ECVM could augment retinal transduction efficiency of intravitreal AAV8-CMV-EGFP in normal rabbit and nonhuman primate (NHP) macaque. Potential mechanisms underlying enhanced retinal transduction by ECVM were also studied. Methods: We applied an electric micro-current across the intact eye of normal rabbit and monkey in vivo for a brief period immediately after intravitreal injection of AAV8-CMV-EGFP. Retinal GFP expression was evaluated by fundus imaging in vivo. Retinal immunohistochemistry was performed to assess the distribution of retinal cells transduced by the AAV8-EGFP. Basic fibroblast growth factor (bFGF) was analyzed by quantitative RT-polymerase chain reaction (PCR). Müller glial reactivity and inner limiting membrane (ILM) were examined by the glial fibrillary acidic protein (GFAP) and vimentin staining in mouse retina, respectively. Results: ECVM significantly increased the efficiency of AAV reaching and transducing the rabbit retina following intravitreal injection, with gene expression in inner nuclear layer, ganglion cells, and Müller cells. Similar trend of improvement was observed in the ECVM-treated monkey eye. The electric micro-current upregulated bFGF expression in Müller cells and vimentin showed ILM structural changes in mouse retina. Conclusions: ECVM promotes the transduction efficiency of AAV8-CMV-GFP in normal rabbit and monkey retinas following intravitreal injection. Translational Relevance: This work has potential translational relevance to human ocular gene therapy by increasing retinal expression of therapeutic vectors given by intravitreal administration.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Dependovirus / Vectores Genéticos Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Transl Vis Sci Technol Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Dependovirus / Vectores Genéticos Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Transl Vis Sci Technol Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos