December 2010
Volume 10, Issue 15
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OSA Fall Vision Meeting Abstract  |   December 2010
AAV-mediated gene delivery to retinal ganglion cells in the macaque eye
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
Author Affiliations
  • Lu Yin
    Flaum Eye Institute, University of Rochester, Rochester, NY, USA
    Center for Visual Science, University of Rochester, Rochester, NY, USA
  • Deniz Dalkara
    Helen Wills Neuroscience Institute, University of California, Berkeley, CA, USA
  • Kenneth Greenberg
    Helen Wills Neuroscience Institute, University of California, Berkeley, CA, USA
    Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA
    Department of Vision Science, University of California, Berkeley, CA, USA
  • Jennifer J. Hunter
    Flaum Eye Institute, University of Rochester, Rochester, NY, USA
  • Benjamin D. Masella
    Helen Wills Neuroscience Institute, University of California, Berkeley, CA, USA
  • Meike Visel
    Helen Wills Neuroscience Institute, University of California, Berkeley, CA, USA
    Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA
    Department of Vision Science, University of California, Berkeley, CA, USA
  • David DiLoreto Jr.
    Flaum Eye Institute, University of Rochester, Rochester, NY, USA
  • John Flannery
    Helen Wills Neuroscience Institute, University of California, Berkeley, CA, USA
    Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA
    Department of Vision Science, University of California, Berkeley, CA, USA
  • David R. Williams
    Center for Visual Science, University of Rochester, Rochester, NY, USA
    Helen Wills Neuroscience Institute, University of California, Berkeley, CA, USA
  • William H. Merigan
    Flaum Eye Institute, University of Rochester, Rochester, NY, USA
    Center for Visual Science, University of Rochester, Rochester, NY, USA
Journal of Vision December 2010, Vol.10, 66. doi:https://doi.org/10.1167/10.15.66
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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. https://doi.org/10.1167/10.15.66.

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Abstract

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.

Acknowledgments
This work was supported by NIH research grants EY019375, BRP-EY014375, and NDC 5PN2EY018241; NIH Training Grant-EY07125; NIH Core Grant-EY001319; NSF Science and Technology Center for Adaptive Optics (Santa Cruz, CA, managed by the University of California at Santa Cruz, cooperative agreement no.: AST-9876783) and Grants from the Foundation Fighting Blindness and Research to Prevent Blindness. 
We thank Jennifer Strazzeri for assistance with surgery and fundus photography, Lee Anne Schery and Robin Sharma for assistance with adaptive optics imaging, and Thurma McDaniel and Tracey Bubel for assistance with histology. 
© 2010 ARVO
Copyright © 2024 Association for Research in Vision and Ophthalmology.
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