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Lu Yin, Deniz Dalkara, Kenneth Greenberg, Jennifer J. Hunter, Benjamin D. Masella, Meike Visel, David DiLoreto Jr., John Flannery, David R. Williams, William H. Merigan; AAV-mediated gene delivery to retinal ganglion cells in the macaque eye. Journal of Vision 2010;10(15):66. doi: 10.1167/10.15.66.
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© ARVO (1962-2015); The Authors (2016-present)
Although adeno-associated virus (AAV) is an effective carrier to insert gene products into retinal ganglion cells (RGCs) in small animals, such as mice, only a few studies have been carried out in macaques, whose retina is more similar to that of humans. We have previously shown that AAV2 with the human connexin 36 (hCx36) promoter can transduce foveal ganglion cells in macaque eyes with great efficiency. Here, we examine for the first time in the macaque two additional AAV serotypes (AAV5 and AAV9 single tyrosine mutant (Y446F)), with the hCx36 promoter carrying green fluorescent protein (GFP) as a fluorescent reporter to determine if they can extend RGC transduction outside the fovea. Fundus photography revealed that AAV5 and AAV9.Y446F transduced macaque foveal ganglion cells as previously observed with AAV2. However unlike AAV2, these vectors also transduced peripheral ganglion cells as shown by GFP expressing axon bundles entering the optic nerve. High-resolution adaptive optics in vivo imaging revealed that AAV5 also sparsely transduced additional cells in the ganglion cell layer that were not visible in fundus images, to a retinal eccentricity of approximately 6 degrees, a significant expansion from that produced by AAV2. Our finding of strong transduction by AAV5 was unanticipated given that AAV5 is ineffective at transducing mouse ganglion cells. Together, our results indicate that AAV vectors have significantly different transduction properties in the macaque retina compared to the rodent retina: an important consideration for ocular gene therapy studies using AAV.
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