April 2010
Volume 51, Issue 13
ARVO Annual Meeting Abstract  |   April 2010
Gene Delivery Efficiency and Specificity of Adeno-Associated Virus Subtypes in the Retina
Author Affiliations & Notes
  • M. T. A. Malik
    Schepens Eye Research Institue, Boston, Massachusetts
  • K.-S. Cho
    Schepens Eye Research Institute, Boston, Massachusetts
  • K. Tchedre
    Schepens Eye Research Institue, Boston, Massachusetts
  • G. Gao
    Umass Medical School, Boston, Massachusetts
  • D. Chen
    Schepens Eye Research Institue, Boston, Massachusetts
  • Footnotes
    Commercial Relationships  M.T.A. Malik, None; K.-S. Cho, None; K. Tchedre, None; G. Gao, None; D. Chen, None.
  • Footnotes
    Support  NIH/NEI R01EY017641, Department of Defense W81XWH-04-2-0008; the American Health Foundation, P30 EY003790 (Core grant to the Schepens Eye Research Institute).
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 3107. doi:
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      M. T. A. Malik, K.-S. Cho, K. Tchedre, G. Gao, D. Chen; Gene Delivery Efficiency and Specificity of Adeno-Associated Virus Subtypes in the Retina. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3107.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : Adeno-associated virus (AAV) is a commonly used gene delivery vehicle for in vivo gene transfer to retinal neurons. Different subtypes of AAVs exhibit various gene delivery efficiency and cell specificity. To select the AAV cassettes that can be used for gene delivery to various retinal cell types in vivo, we tested the patterns and infection efficiencies of a wide range of AAV subtypes which carry an enhance green fluorescence protein (EGFP) gene in the mouse eyes. We also examined gene expression profiles of AAVs in retinal ganglion cell axons, optic tracts, and their central targets in the brain.

Methods: : At least 9 different subtypes of AAVs carrying EGFP were injected into the vitreous of adult mice. Two weeks after injection, animal were sacrificed. The retina, optic nerve, and brains were dissected and fixed in 4 % paraformaldehyde. The eyeballs and optic nerves were sectioned with a cryotate, and AAV infected cells were examined under a fluorescent microscope. Vibratome sections of the mouse brains were also prepared and analyzed under a fluorescent microscope.

Results: : Among the total of 9 subtypes of AAVs examined, we found that AAV9 specifically infected photoreceptor cells with a high efficiency. AAV10 also specifically targeted photoreceptor cells but was limited to a very small area near the injection site. AAV2 primarily infected cells in the ganglion cell layer and Muller cells. EGFP labeling was also seen in several AAV infected mice along the optic nerve fibers and optic tracts, and reaching the central targets in the brain, including the lateral geniculate nuclei. AAV6 drove a similar pattern of gene expression as AAV2 but was also seen with less efficiency.

Conclusions: : Our data suggest that AAV2 and AAV9 may be used as appropriate vehicles for transferring specific genes to its required destination to retinal ganglion cells, Muller cells, or photoreceptor cells. Identification of the subtype of AAVs that selectively deliver genes to a single cell population with a high efficiency in the retina is important for future design of gene therapy to treat various retinal neurodegenerative diseases.

Keywords: gene transfer/gene therapy • optic nerve • adenovirus 

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