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Tae Kwann Park, Si Hyung Lee, Ye Seul Kim, Seung Kwan Nah, Young-Hoon Ohn; Transduction Patterns of an Adeno-associated Viral Vector in a Laser-induced Choroidal Neovascularization Mouse Model. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2635.
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This study investigated the patterns of transduction of adeno-associated virus (AAV) 2, 5, and 8 vectors in laser-induced choroidal neovascularization (CNV) murine model and compared their transduction efficacy.
C57BL/6J mice were subjected to bilateral laser photocoagulation to develop CNVs 5 days prior to unilateral intravitreal injection of AAV type 2, 5 and 8 capsids expressing EGFP. All eyes were enucleated 7 days after injection and examined with immunohistochemistry using various antibodies for indentification of transduced cells and quantitative image analysis was performed.
CNV formation resulted in robustly increased transduction around the CNV lesions for all AAV capsid types, AAV2 with most increased transduction. Without CNV formation, AAV2 vector transduced ganglion cells and cells in inner nuclear layer (INL) and AAV5 and 8 transduced only a small portion of cells in retinal ganglion cell layer. CNV formation increased AAV2 vector expression throughout the retina and in and around CNVs, and transduced cells included retinal ganglion cell, Müller cells, cells in INL and outer nuclear layer (ONL), photoreceptors, and retinal pigment epithelium (RPE). Inflammatory cells and endothelial cells in CNVs were also effectively transduced by AAV2. AAV5 and AAV8 vector demonstrated transduction in retinal ganglion cells, Müller cells, INL cells, ONL cells, and RPE in a localized pattern, and only endothelial cells at the surface of CNV showed EGFP expression.
Enhanced transduction of AAV2, 5, and 8 was achieved upon CNV formation, and AAV2 showed most effective transduction in cells in CNV lesions, including inflammatory cells and endothelial cells.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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