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Assessment of Structure and Function Over a 3-year Period after Gene Transfer in RPE65−/− dogs

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Abstract

Aim: To assess retinal structure and function over a 3-year period in a group of five RPE65−/− dogs treated by unilateral rAAV- mediated subretinal gene transfer. Methods: Post-operative functional follow-ups were performed using simultaneous, bilateral, full-field ERGs. Structure was evaluated by SLO using FL and ICG angiography and by EM. Results: Significant improvement of retinal function was observed through ERGs approximately 4 weeks following surgery. Scotopic b-wave amplitudes peaked 3 months after surgery. Then there was a successive reduction, although greater amplitudes than base-line values were observed at all post-operative time points. A-wave amplitudes increased at a later time than b-wave amplitudes and were sustained throughout the follow-up period. The increased cone function was preserved longer than the rod function. Angiography showed structural changes at the site of injection, corroborated by photoreceptor destruction observed ultrastructurally. Immediately adjacent to the subretinal injection area photoreceptor outer segments appeared normal. Conclusion: Despite local structural alterations at the subretinal injection site, subretinal gene transfer in the RPE65 null mutation dog effectively increases retinal function for at least 3 years after surgery.

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Abbreviations

EM:

electron microscopy

FL:

fluorescein

GFP:

green fluorescent protein

ICG:

indocyanine green

LCA:

Leber’s congenital amaurosis

rAAV:

recombinant Adeno-associated Virus

RPE:

retinal pigment epithelium

SLO:

scanning laser ophthalmoscopy

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Authors and Affiliations

  1. College of Veterinary Medicine, University of Missouri-Columbia, Columbia, MO, USA

    Kristina Narfström

  2. Mason Eye Institute, University of Missouri-Columbia, MO, USA

    Kristina Narfström & Martin Katz

  3. School of Optometry, University of New South Wales, Australia

    Vaegan

  4. VisionTest Australia, Sydney, Australia

    Vaegan

  5. Ulleval University Hospital, Oslo, Norway

    Ragnheidur Bragadottir

  6. Centre for Ophthalmology and Visual Science, University of Western Australia, Nedlands, Australia

    Elizabeth P. Rakoczy

  7. University Eye Hospital, Tuebingen, Germany

    Mathias Seeliger

  8. Department of Veterinary Medicine and Surgery, A379 Clydesdale Hall, Columbia, MO, 65211, USA

    Kristina Narfström

Authors
  1. Kristina Narfström
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  2. Vaegan
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  3. Martin Katz
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  4. Ragnheidur Bragadottir
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  5. Elizabeth P. Rakoczy
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  6. Mathias Seeliger
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Corresponding author

Correspondence to Kristina Narfström.

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Narfström, K., Vaegan, Katz, M. et al. Assessment of Structure and Function Over a 3-year Period after Gene Transfer in RPE65−/− dogs. Doc Ophthalmol 111, 39–48 (2005). https://doi.org/10.1007/s10633-005-3159-0

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  • DOI: https://doi.org/10.1007/s10633-005-3159-0

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