April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Outer Retinal Transduction Can Be Achieved Following Intravitreal Delivery Of AAV2 In Conjunction With Glycosidic Enzymes
Author Affiliations & Notes
  • Jasmina Cehajic Kapetanovic
    Faculty of Medical and Human Sciences,
    University of Manchester, Manchester, United Kingdom
  • Magali M. Le Goff
    Faculty of Medical and Human Sciences,
    University of Manchester, Manchester, United Kingdom
  • Annette Allen
    Faculty of Life Sciences,
    University of Manchester, Manchester, United Kingdom
  • Robert J. Lucas
    Faculty of Life Sciences,
    University of Manchester, Manchester, United Kingdom
  • Paul N. Bishop
    Faculty of Medical and Human Sciences,
    University of Manchester, Manchester, United Kingdom
  • Footnotes
    Commercial Relationships  Jasmina Cehajic Kapetanovic, None; Magali M. Le Goff, None; Annette Allen, None; Robert J. Lucas, None; Paul N. Bishop, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 1406. doi:
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      Jasmina Cehajic Kapetanovic, Magali M. Le Goff, Annette Allen, Robert J. Lucas, Paul N. Bishop; Outer Retinal Transduction Can Be Achieved Following Intravitreal Delivery Of AAV2 In Conjunction With Glycosidic Enzymes. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1406.

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

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Abstract

Purpose: : At present only limited retinal transduction can be achieved following intravitreal delivery of AAV vectors. We hypothesized that the vitreous, inner limiting lamina, retinal extracellular matrix and cell surface proteoglycans pose physical barriers to tissue penetration by the vector particles from the vitreous. In this study we investigated the effects of enzymatic digestion of these barriers on the depth of vector penetration into the retina.

Methods: : The green fluorescent protein (GFP)-expressing AAV2 vector was co-injected intravitreally with chondroitin ABC lyase or heparinase III at their optimal concentration. The efficacy of the virus transduction was evaluated after two weeks by visualizing fluorescence in histological cross-sections using fluorescent microscopy. We also analyzed safety of these treatments and retinal function using electroretinography.

Results: : Both chondroitin ABC lyase and heparinase III led to a significant improvement in retinal transduction following intravitreal delivery. These enzymes both markedly improved transduction of the outer retina, including photoreceptor cells. Electroretinograms survived at much higher doses of enzymes than were needed for optimal retinal transduction.

Conclusions: : AAV2-mediated retinal transduction is improved by co-injection of heparinase III or chondroitin ABC lyase. Improved transduction efficiency may allow intravitreal injection to become the preferred route for delivering gene therapy to both the inner and outer retina.

Keywords: adenovirus • retina • gene transfer/gene therapy 
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