Documenta Ophthalmologica

, Volume 111, Issue 1, pp 39–48

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

  • Kristina Narfström
  • Vaegan
  • Martin Katz
  • Ragnheidur Bragadottir
  • Elizabeth P. Rakoczy
  • Mathias Seeliger

DOI: 10.1007/s10633-005-3159-0

Cite this article as:
Narfström, K., Vaegan, Katz, M. et al. Doc Ophthalmol (2005) 111: 39. doi:10.1007/s10633-005-3159-0


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.


dog gene transfer retinal dystrophy Leber’s congenital amaurosis rAAV RPE65 



electron microscopy




green fluorescent protein


indocyanine green


Leber’s congenital amaurosis


recombinant Adeno-associated Virus


retinal pigment epithelium


scanning laser ophthalmoscopy

Copyright information

© Springer 2006

Authors and Affiliations

  • Kristina Narfström
    • 1
    • 2
    • 8
  • Vaegan
    • 3
    • 4
  • Martin Katz
    • 2
  • Ragnheidur Bragadottir
    • 5
  • Elizabeth P. Rakoczy
    • 6
  • Mathias Seeliger
    • 7
  1. 1.College of Veterinary MedicineUniversity of Missouri-ColumbiaColumbiaUSA
  2. 2.Mason Eye InstituteUniversity of Missouri-ColumbiaUSA
  3. 3.School of OptometryUniversity of New South WalesAustralia
  4. 4.VisionTest AustraliaSydneyAustralia
  5. 5.Ulleval University HospitalOsloNorway
  6. 6.Centre for Ophthalmology and Visual ScienceUniversity of Western AustraliaNedlandsAustralia
  7. 7.University Eye HospitalTuebingenGermany
  8. 8.Department of Veterinary Medicine and SurgeryColumbiaUSA

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