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Vitreal delivery of AAV vectored Cnga3 restores cone function in CNGA3-/-/Nrl-/- mice, an all-cone model of CNGA3 achromatopsia.
Du, Wei; Tao, Ye; Deng, Wen-Tao; Zhu, Ping; Li, Jie; Dai, Xufeng; Zhang, Yuxin; Shi, Wei; Liu, Xuan; Chiodo, Vince A; Ding, Xi-Qin; Zhao, Chen; Michalakis, Stylianos; Biel, Martin; Zhang, Zuoming; Qu, Jia; Hauswirth, William W; Pang, Ji-Jing.
Afiliación
  • Du W; Deparment of Ophthalmology, University of Florida, Gainesville, FL 32610, USA.
  • Tao Y; Deparment of Ophthalmology, University of Florida, Gainesville, FL 32610, USA.
  • Deng WT; Deparment of Ophthalmology, University of Florida, Gainesville, FL 32610, USA.
  • Zhu P; Deparment of Ophthalmology, University of Florida, Gainesville, FL 32610, USA.
  • Li J; Deparment of Ophthalmology, University of Florida, Gainesville, FL 32610, USA.
  • Dai X; Deparment of Ophthalmology, University of Florida, Gainesville, FL 32610, USA, School of Ophthalmology and Optometry, The Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
  • Zhang Y; Deparment of Ophthalmology, University of Florida, Gainesville, FL 32610, USA, Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University and State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China.
  • Shi W; Deparment of Ophthalmology, University of Florida, Gainesville, FL 32610, USA.
  • Liu X; Deparment of Ophthalmology, University of Florida, Gainesville, FL 32610, USA.
  • Chiodo VA; Deparment of Ophthalmology, University of Florida, Gainesville, FL 32610, USA.
  • Ding XQ; Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
  • Zhao C; Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University and State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China.
  • Michalakis S; Munich Center for Integrated Protein Science and Department of Pharmacy, Center for Drug Research, Ludwig-Maximilians-Universität München, 81377 Munich, Germany and.
  • Biel M; Munich Center for Integrated Protein Science and Department of Pharmacy, Center for Drug Research, Ludwig-Maximilians-Universität München, 81377 Munich, Germany and.
  • Zhang Z; Department of Clinical Aerospace Medicine, Fourth Military Medical University, Xi'an 710032, China jpang@ufl.edu.
  • Qu J; School of Ophthalmology and Optometry, The Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China, jpang@ufl.edu.
  • Hauswirth WW; Deparment of Ophthalmology, University of Florida, Gainesville, FL 32610, USA, jpang@ufl.edu.
  • Pang JJ; Deparment of Ophthalmology, University of Florida, Gainesville, FL 32610, USA, School of Ophthalmology and Optometry, The Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China, Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University and State Key
Hum Mol Genet ; 24(13): 3699-707, 2015 Jul 01.
Article en En | MEDLINE | ID: mdl-25855802
ABSTRACT
The CNGA3(-/-)/Nrl(-/-) mouse is a cone-dominant model with Cnga3 channel deficiency, which partially mimics the all cone foveal structure of human achromatopsia 2 with CNGA3 mutations. Although subretinal (SR) AAV vector administration can transfect retinal cells efficiently, the injection-induced retinal detachment can cause retinal damage, particularly when SR vector bleb includes the fovea. We therefore explored whether cone function-structure could be rescued in CNGA3(-/-)/Nrl(-/-) mice by intravitreal (IVit) delivery of tyrosine to phenylalanine (Y-F) capsid mutant AAV8. We find that AAV-mediated CNGA3 expression can restore cone function and rescue structure following IVit delivery of AAV8 (Y447, 733F) vector. Rescue was assessed by restoration of the cone-mediated electroretinogram (ERG), optomotor responses, and cone opsin immunohistochemistry. Demonstration of gene therapy in a cone-dominant mouse model by IVit delivery provides a potential alternative vector delivery mode for safely transducing foveal cones in achromatopsia patients and in other human retinal diseases affecting foveal function.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Terapia Genética / Defectos de la Visión Cromática / Células Fotorreceptoras Retinianas Conos / Factores de Transcripción con Cremalleras de Leucina de Carácter Básico / Proteínas del Ojo / Canales Catiónicos Regulados por Nucleótidos Cíclicos Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans / Male Idioma: En Revista: Hum Mol Genet Asunto de la revista: BIOLOGIA MOLECULAR / GENETICA MEDICA Año: 2015 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Terapia Genética / Defectos de la Visión Cromática / Células Fotorreceptoras Retinianas Conos / Factores de Transcripción con Cremalleras de Leucina de Carácter Básico / Proteínas del Ojo / Canales Catiónicos Regulados por Nucleótidos Cíclicos Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans / Male Idioma: En Revista: Hum Mol Genet Asunto de la revista: BIOLOGIA MOLECULAR / GENETICA MEDICA Año: 2015 Tipo del documento: Article País de afiliación: Estados Unidos