April 2011
Volume 52, Issue 14
ARVO Annual Meeting Abstract  |   April 2011
efficiency And Specificity Of Gene Delivery To The Retina And Optic Tracts By Adeno-associated Virus
Author Affiliations & Notes
  • Muhammad Taimur A. Malik
    Schepens Eye Research Institue, Boston, Massachusetts
  • Kin-Sang Cho
    Schepens Eye Research Institute, Boston, Massachusetts
  • Guangping Gao
    Gene Therapy and Vector Core, University of Massachusetts Medical School, Worcester, Massachusetts
  • Kissaou Tchedre
    Schepens Eye Research Institue, Boston, Massachusetts
  • Dong Feng Chen
    Schepens Eye Research Institue, Boston, Massachusetts
    VA Center for innovative Visual Rehabilitation, VA Boston Health Care System, Boston, Massachusetts
  • Footnotes
    Commercial Relationships  Muhammad Taimur A. Malik, None; Kin-Sang Cho, None; Guangping Gao, None; Kissaou Tchedre, None; Dong Feng Chen, None
  • Footnotes
    Support  NIH/NEI R01EY017641, Department of Defense W81XWH-04-2-0008
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 1408. doi:
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      Muhammad Taimur A. Malik, Kin-Sang Cho, Guangping Gao, Kissaou Tchedre, Dong Feng Chen; efficiency And Specificity Of Gene Delivery To The Retina And Optic Tracts By Adeno-associated Virus. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1408.

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

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Purpose: : Adeno-associated virus (AAV) is a promising gene delivery vehicle for the retina because of its ability to transduce genes to post-mitotic cells efficiently for long period with minimal cytoxicity. Different subtypes of AAVs exhibit different gene delivery efficiency, cell specificity and duration of effect. The purpose of the present study is to determine the subtypes of AAVs for their transfection efficiency and specificity in retina and optic nerve.

Methods: : AAV subtypes carrying an enhanced green fluorescence protein (AAV-EGFP) were intravitreally injected into the right eye of adult C57BL6 mice. The mice were sacrificed at four to thirteen weeks post injection. Their eyeballs, optic nerves, and brains were dissected and fixed in 4 % Paraformaldehyde. The eyeball along with the optics nerve were cryosectioned at 10 um thickness. Double immunofluorescence labeling of GFP and primary antibodies recognizing specific retinal cell markers were performed to determine the gene delivery specificity. Gene tranduction efficiency of AAV in the brain and retina was evaluated in coronal sections of the mouse brains and retinas.

Results: : The gene transduction efficiency of various AAV subtypes was seen to reach the plateau after week 4. Different AAV subtypes exhibit different selectivity for targeted gene delivery. AAV2 delivered gene to the inner nuclear layer, including Muller glia and retinal ganglion cells. Moreover, AAV2-EGFP expression was detectable in the optic nerve fibers, optic tracts and the central visual targets including the lateral geneticulate nuclei and superior colliculus. Incontrast , the AAV 6 and AAV9 showed strong expression patterns in the outer nuclear layer, mostly photoreceptor cells without affecting the rest of the retinal layers. Quantification of the numbers of cells infected, we noted that the expression in AAV 2-EGFP was close to 70% cells in the GCL and INL, while AAV6 and AAV9 transduce 60% and 70% cells in the ONL respectively

Conclusions: : Our data indicate that different subtypes of AAVs can be designed as a delivery vehicle, targeting different retinal cell populations, including retinal ganglion cells or photoreceptors, respectively

Keywords: gene transfer/gene therapy • retina • retina: distal (photoreceptors, horizontal cells, bipolar cells) 

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