Transduction Patterns of Adeno-associated Viral Vectors in a Laser-Induced Choroidal Neovascularization Mouse Model
Adeno-associated virus (AAV) vector is a promising platform technology for ocular gene therapy. Recently clinical successes to treat choroidal neovascularization (CNV) in wet type age-related macular degeneration have been reported. However, because pathologic conditions of the retina may alter the...
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| Format: | Article |
| Language: | English |
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Elsevier
2018-06-01
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| Series: | Molecular Therapy: Methods & Clinical Development |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2329050118300093 |
| _version_ | 1818971888277258240 |
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| author | Si Hyung Lee Ye Seul Kim Seung Kwan Nah Hee Jong Kim Ha Yan Park Jin Young Yang Keerang Park Tae Kwann Park |
| author_facet | Si Hyung Lee Ye Seul Kim Seung Kwan Nah Hee Jong Kim Ha Yan Park Jin Young Yang Keerang Park Tae Kwann Park |
| author_sort | Si Hyung Lee |
| collection | DOAJ |
| description | Adeno-associated virus (AAV) vector is a promising platform technology for ocular gene therapy. Recently clinical successes to treat choroidal neovascularization (CNV) in wet type age-related macular degeneration have been reported. However, because pathologic conditions of the retina may alter the tropism of viral vectors, it is necessary to evaluate the transduction efficiency of different serotypes of AAV vectors in the retinas with CNVs. Here, we show the patterns and efficacy of transduction of AAV2, -5, and -8 vectors in a laser-induced CNV mouse model. C57BL/6J mice were subjected to unilateral laser photocoagulation on the right eye to induce CNV 5 days prior to intravitreal injection of AAV2, -5, and -8 capsids expressing EGFP. Transduction was increased around CNV lesions for all AAV capsid types, and AAV2 resulted in the highest transduction efficiency. In the absence of CNV, the AAV2 vector transduced ganglion and inner nuclear layer (INL) cells, and AAV5 and AAV8 transduced only a small proportion of cells in the retinal ganglion cell layer. CNV increased AAV2 vector expression throughout the retina and in and around CNVs; the transduced cells included retinal ganglion cells, Müller cells, cells from the INL and outer nuclear layer (ONL), photoreceptors, and retinal pigment epithelium (RPE) cells. Inflammatory cells and endothelial cells in CNVs were also transduced by AAV2. AAV5 and AAV8 were transduced in retinal ganglion, Müller, INL, ONL, and RPE cells in a localized pattern, and only endothelial cells at the surface of CNV lesions showed EGFP expression. Taken together, CNV formation resulted in enhanced transduction of AAV2, -5, and -8, and AAV2 exhibited the highest transduction efficiency in cells in CNV lesions. Keywords: adeno-associated virus, choroidal neovascularization, age-related macular generation, gene therapy |
| first_indexed | 2024-12-20T14:59:32Z |
| format | Article |
| id | doaj.art-fc70f61e14e34c35a1e7407e9bdcafdc |
| institution | Directory Open Access Journal |
| issn | 2329-0501 |
| language | English |
| last_indexed | 2024-12-20T14:59:32Z |
| publishDate | 2018-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Methods & Clinical Development |
| spelling | doaj.art-fc70f61e14e34c35a1e7407e9bdcafdc2022-12-21T19:36:42ZengElsevierMolecular Therapy: Methods & Clinical Development2329-05012018-06-0199098Transduction Patterns of Adeno-associated Viral Vectors in a Laser-Induced Choroidal Neovascularization Mouse ModelSi Hyung Lee0Ye Seul Kim1Seung Kwan Nah2Hee Jong Kim3Ha Yan Park4Jin Young Yang5Keerang Park6Tae Kwann Park7Department of Ophthalmology, Soonchunhyang University, College of Medicine, Cheonan 31151, Republic of Korea; Department of Ophthalmology, Soonchunhyang University Hospital Bucheon, Bucheon 14584, Republic of KoreaDepartment of Ophthalmology, Soonchunhyang University, College of Medicine, Cheonan 31151, Republic of Korea; Department of Ophthalmology, Soonchunhyang University Hospital Bucheon, Bucheon 14584, Republic of KoreaDepartment of Ophthalmology, Soonchunhyang University, College of Medicine, Cheonan 31151, Republic of Korea; Department of Ophthalmology, Soonchunhyang University Hospital Bucheon, Bucheon 14584, Republic of KoreaCdmogen Co., Ltd., Cheongju 28751, Republic of KoreaDepartment of Ophthalmology, Soonchunhyang University Hospital Bucheon, Bucheon 14584, Republic of KoreaDepartment of Ophthalmology, Soonchunhyang University Hospital Bucheon, Bucheon 14584, Republic of KoreaDepartment of Biopharmacy, Chungbuk Health & Science University, Cheongju, Chungbuk 28150, Republic of KoreaDepartment of Ophthalmology, Soonchunhyang University, College of Medicine, Cheonan 31151, Republic of Korea; Department of Ophthalmology, Soonchunhyang University Hospital Bucheon, Bucheon 14584, Republic of Korea; Corresponding author: Tae Kwann Park, MD, PhD, Department of Ophthalmology, Soonchunhyang University Hospital Bucheon, 170 Jomaru-ro, Wonmi-gu, Bucheon 14584, Republic of Korea.Adeno-associated virus (AAV) vector is a promising platform technology for ocular gene therapy. Recently clinical successes to treat choroidal neovascularization (CNV) in wet type age-related macular degeneration have been reported. However, because pathologic conditions of the retina may alter the tropism of viral vectors, it is necessary to evaluate the transduction efficiency of different serotypes of AAV vectors in the retinas with CNVs. Here, we show the patterns and efficacy of transduction of AAV2, -5, and -8 vectors in a laser-induced CNV mouse model. C57BL/6J mice were subjected to unilateral laser photocoagulation on the right eye to induce CNV 5 days prior to intravitreal injection of AAV2, -5, and -8 capsids expressing EGFP. Transduction was increased around CNV lesions for all AAV capsid types, and AAV2 resulted in the highest transduction efficiency. In the absence of CNV, the AAV2 vector transduced ganglion and inner nuclear layer (INL) cells, and AAV5 and AAV8 transduced only a small proportion of cells in the retinal ganglion cell layer. CNV increased AAV2 vector expression throughout the retina and in and around CNVs; the transduced cells included retinal ganglion cells, Müller cells, cells from the INL and outer nuclear layer (ONL), photoreceptors, and retinal pigment epithelium (RPE) cells. Inflammatory cells and endothelial cells in CNVs were also transduced by AAV2. AAV5 and AAV8 were transduced in retinal ganglion, Müller, INL, ONL, and RPE cells in a localized pattern, and only endothelial cells at the surface of CNV lesions showed EGFP expression. Taken together, CNV formation resulted in enhanced transduction of AAV2, -5, and -8, and AAV2 exhibited the highest transduction efficiency in cells in CNV lesions. Keywords: adeno-associated virus, choroidal neovascularization, age-related macular generation, gene therapyhttp://www.sciencedirect.com/science/article/pii/S2329050118300093 |
| spellingShingle | Si Hyung Lee Ye Seul Kim Seung Kwan Nah Hee Jong Kim Ha Yan Park Jin Young Yang Keerang Park Tae Kwann Park Transduction Patterns of Adeno-associated Viral Vectors in a Laser-Induced Choroidal Neovascularization Mouse Model Molecular Therapy: Methods & Clinical Development |
| title | Transduction Patterns of Adeno-associated Viral Vectors in a Laser-Induced Choroidal Neovascularization Mouse Model |
| title_full | Transduction Patterns of Adeno-associated Viral Vectors in a Laser-Induced Choroidal Neovascularization Mouse Model |
| title_fullStr | Transduction Patterns of Adeno-associated Viral Vectors in a Laser-Induced Choroidal Neovascularization Mouse Model |
| title_full_unstemmed | Transduction Patterns of Adeno-associated Viral Vectors in a Laser-Induced Choroidal Neovascularization Mouse Model |
| title_short | Transduction Patterns of Adeno-associated Viral Vectors in a Laser-Induced Choroidal Neovascularization Mouse Model |
| title_sort | transduction patterns of adeno associated viral vectors in a laser induced choroidal neovascularization mouse model |
| url | http://www.sciencedirect.com/science/article/pii/S2329050118300093 |
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