Recombinant adeno-associated virus type 2-mediated gene delivery into the Rpe65-/-knockout mouse eye results in limited rescue
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Lai, Chooi May, et al. Recombinant Adeno-associated Virus Type 2-mediated Gene Delivery Into the Rpe65-/-knockout Mouse Eye Results In Limited Rescue. BioMed Central Ltd, 2004. https://doi.org/10.17615/nqhg-8h33APA
Lai, C., Yu, M., Brankov, M., Barnett, N., Zhou, X., Redmond, T., Narfstrom, K., & Rakoczy, P. (2004). Recombinant adeno-associated virus type 2-mediated gene delivery into the Rpe65-/-knockout mouse eye results in limited rescue. BioMed Central Ltd. https://doi.org/10.17615/nqhg-8h33Chicago
Lai, Chooi May, Meaghan Jt Yu, Meliha Brankov, Nigel L Barnett, Xiaohuai Zhou, T Michael Redmond, Kristina Narfstrom et al. 2004. Recombinant Adeno-Associated Virus Type 2-Mediated Gene Delivery Into the Rpe65-/-Knockout Mouse Eye Results In Limited Rescue. BioMed Central Ltd. https://doi.org/10.17615/nqhg-8h33- Creator
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Lai, Chooi-May
- Other Affiliation: Centre for Ophthalmology and Visual Science, The University of Western Australia, Perth, Western Australia, 6009, Australia
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Yu, Meaghan JT
- Other Affiliation: Department of Molecular Ophthalmology, Lions Eye Institute and The University of Western Australia, Perth, Western Australia, 6009, Australia
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Brankov, Meliha
- Other Affiliation: Department of Molecular Ophthalmology, Lions Eye Institute and The University of Western Australia, Perth, Western Australia, 6009, Australia
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Barnett, Nigel L
- Other Affiliation: Vision Touch and Hearing Research Centre, School of Biomedical Sciences, University of Queensland, Brisbane, Queensland, 4072, Australia
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Zhou, Xiaohuai
- Affiliation: School of Medicine, Gene Therapy Center
- Other Affiliation: UNC Vector Core
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Redmond, T Michael
- Other Affiliation: Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, National Institutes of Health, Bethesda, Maryland, 20892, USA
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Narfstrom, Kristina
- Other Affiliation: Vision Science Group, Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri-Columbia, Columbia, Missouri, 65211, USA
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Rakoczy, P Elizabeth
- Other Affiliation: Centre for Ophthalmology and Visual Science, The University of Western Australia, Perth, Western Australia, 6009, Australia
- Abstract
- Abstract Background Leber's congenital amaurosis (LCA) is a severe form of retinal dystrophy. Mutations in the RPE65 gene, which is abundantly expressed in retinal pigment epithelial (RPE) cells, account for approximately 10–15% of LCA cases. In this study we used the high turnover, and rapid breeding and maturation time of the Rpe65-/- knockout mice to assess the efficacy of using rAAV-mediated gene therapy to replace the disrupted RPE65 gene. The potential for rAAV-mediated gene treatment of LCA was then analyzed by determining the pattern of RPE65 expression, the physiological and histological effects that it produced, and any improvement in visual function. Methods rAAV.RPE65 was injected into the subretinal space of Rpe65-/- knockout mice and control mice. Histological and immunohistological analyses were performed to evaluate any rescue of photoreceptors and to determine longevity and pattern of transgene expression. Electron microscopy was used to examine ultrastructural changes, and electroretinography was used to measure changes in visual function following rAAV.RPE65 injection. Results rAAV-mediated RPE65 expression was detected for up to 18 months post injection. The delivery of rAAV.RPE65 to Rpe65-/- mouse retinas resulted in a transient improvement in the maximum b-wave amplitude under both scotopic and photopic conditions (76% and 59% increase above uninjected controls, respectively) but no changes were observed in a-wave amplitude. However, this increase in b-wave amplitude was not accompanied by any slow down in photoreceptor degeneration or apoptotic cell death. Delivery of rAAV.RPE65 also resulted in a decrease in retinyl ester lipid droplets and an increase in short wavelength cone opsin-positive cells, suggesting that the recovery of RPE65 expression has long-term benefits for retinal health. Conclusion This work demonstrated the potential benefits of using the Rpe65-/- mice to study the effects and mechanism of rAAV.RPE65-mediated gene delivery into the retina. Although the functional recovery in this model was not as robust as in the dog model, these experiments provided important clues about the long-term physiological benefits of restoration of RPE65 expression in the retina.
- Date of publication
- April 27, 2004
- DOI
- Identifier
- Resource type
- Article
- Rights statement
- In Copyright
- Rights holder
- Chooi-May Lai et al.; licensee BioMed Central Ltd.
- Journal title
- Genetic Vaccines and Therapy
- Journal volume
- 2
- Journal issue
- 1
- Page start
- 3
- Language
- English
- Is the article or chapter peer-reviewed?
- Yes
- ISSN
- 1479-0556
- Bibliographic citation
- Genetic Vaccines and Therapy. 2004 Apr 27;2(1):3
- Publisher
- BioMed Central Ltd
- Access right
- Open Access
- Date uploaded
- September 5, 2012
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