May 2003
Volume 44, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2003
Assessment of Bilateral Long-term Electroretinographic Effects following Unilateral rAAV.RPE65 Gene Transfer in Null Mutation Dogs
Author Affiliations & Notes
  • R. Bragadottir
    Department of Ophthalmology, Ullevaal University Hospital, Oslo, Norway
  • M. Ford
    Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri-Columbia, Columbia, MO, United States
  • K. Narfstrom
    Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri-Columbia, Columbia, MO, United States
  • Footnotes
    Commercial Relationships  R. Bragadottir, None; M. Ford, None; K. Narfstrom, None.
  • Footnotes
    Support  Supported by the Foundation Fighting Blindness
Investigative Ophthalmology & Visual Science May 2003, Vol.44, 3590. doi:
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      R. Bragadottir, M. Ford, K. Narfstrom; Assessment of Bilateral Long-term Electroretinographic Effects following Unilateral rAAV.RPE65 Gene Transfer in Null Mutation Dogs . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3590.

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

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Abstract

Abstract: : Purpose: Following unilateral gene transfer in 11 of 12 treated RPE-/- dogs using rAAV.RPE65, significantly increased scotopic and photopic electroretinographic (ERG) responses were found in the treated eye at short-term follow-up (3 mo). The present study reports the results of long-term follow-up ERG studies (up to 12 mo) in a sub-group of these dogs. Methods: : Five RPE65-/- dogs, aged 4-30 mo were included, that all had received similar volumes of the gene construct subretinally into the right eye (OD) and were either not treated (n=1) or injected with an rAAV construct containing Green Fluorescent Protein (GFP) into the contralateral eye (OS) (n=4). Bilateral, simultaneous full-field flash ERGs were performed pre-operatively and at regular intervals using scotopic low and high light intensity stimuli, photopic high intensity and flicker recordings. Mean ERG amplitudes were obtained and paired t-test used for statistical analysis of amplitude changes pre-operatively and up to 9-12 mo post-surgery for both eyes in each treated animal. Results: : Significantly increased ERG a- and b-wave amplitudes were observed in OD throughout the post-operative testing period over pre-operative recordings. No significant changes were observed at 3 mo post surgery in OS, the eye that had not received the gene transfer. At 6 mo, however, there were significant increases in photopic single flash and 30 Hz flicker responses, also in OS. This increase was reduced at 9-12 mo but was still well above base-line parameters. Conclusions: There was no reduction in function as recorded by ERG 3-12 mo post-surgery in the eye that had undergone gene transfer (OD). For the fellow eye, effects were also observed in the photopic responses, starting 6 mo post-surgery. Although reduced at 9-12 mo, they were still above base-line pre-operative levels. These findings demonstrate a positive effect on scotopic and photopic ERG function in the treated eye and suggest a positive influence also on the fellow eye. The mechanism by which the latter event occurs is unclear.

Keywords: electrophysiology: clinical • gene transfer/gene therapy • animal model 
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