| Literature DB >> 25855802 |
Wei Du1, Ye Tao1, Wen-Tao Deng1, Ping Zhu1, Jie Li1, Xufeng Dai2, Yuxin Zhang3, Wei Shi1, Xuan Liu1, Vince A Chiodo1, Xi-Qin Ding4, Chen Zhao5, Stylianos Michalakis6, Martin Biel6, Zuoming Zhang7, Jia Qu8, William W Hauswirth9, Ji-Jing Pang10.
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.Entities:
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Year: 2015 PMID： 25855802 PMCID： PMC4459390 DOI： 10.1093/hmg/ddv114
Source DB: PubMed Journal: Hum Mol Genet ISSN： 0964-6906 Impact factor: 6.150