Advertisement

of the Retina in the 4 Years Following rAAV-mediated Gene Transfer in the RPE65 Null Mutation Dog

  • Kristina Narfstrô m
  • Mathias Seeliger
  • Chooi-May Lai
  • Vaegan
  • Martin Katz
  • Elizabeth P. Rakoczy
  • Charlotte Remé
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 613)

Retinal gene transfer studies performed in our laboratories in groups of 4–42 monthold RPE65 null mutation dogs have shown remarkable functional improvement following a single unilateral subretinal injection of a recombinant adeno-associated virus vector, serotype 2, rAAV2/2, cDNA for dog RPE65 with a cytomegalo virus (CMV) promoter (Narfström et al., 2003a,b, 2005; Ford et al., 2003). The purpose of the present investigation was to further assess long-term therapeutic effects of the gene transfer performed in a group of young RPE65 null mutation dogs and to correlate the functional effects of therapy to morphologic findings up to 4 years following the gene transfer. In addition, retinas of affected dogs were examined for histologic correlates of spots and color changes seen by ophthalmoscopy in both treated and untreated affected dogs.

Keywords

Gene Transfer Outer Nuclear Layer Photoreceptor Outer Segment Severe Degenerative Change Childhood Blindness 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Acland G.M, Aguirre, G.D., Bennett, J., Aleman, T.S., et al., 2006, Long-term restoration of rod and cone vision by single dose rAAV-mediated gene transfer to the retina in a canine model of childhood blindness, Mol Therapy, 12: 1072–1082.CrossRefGoogle Scholar
  2. Acland G.M., Aguirre, G.D., Ray, J., et al., 2001, Gene therapy restores vision in a canine model of childhood blindness, Nat Genet, 28: 92–95.PubMedCrossRefGoogle Scholar
  3. Ford, M., Bragadottir, R., Rakoczy, P.E., Narfströ m, K., 2003, Gene transfer in the RPE65 null mutation dog: relationship between construct volume, visual behaviour and electroretinographic (ERG) results,Doc Ophthalamol, 107: 79–86.CrossRefGoogle Scholar
  4. Guerin, C.J., Lewis, G.P., Fisher, S.K., Anderson, D.H., 1993, Recovery of photoreceptor outer segment length and analysis of membrane assembly rates in regenerating primate photoreceptor outer segments, Invest Ophthalmol Vis Sci, 34: 175–183.PubMedGoogle Scholar
  5. Ivert, L., Kjeldbye, H., Gouras, P., 2002, Long-term effects of short-term retinal bleb detachments in rabbits. Graefe’s Archive Clin Exp Ophthalmol 240: 232–237.CrossRefGoogle Scholar
  6. Le Meur, G., Stieger, K., Weber, M., Deschamps, J.Y., et al., 2006,Restoration of vision in RPE65-deficient Briard dogs using an AAV-serotype 4 vector that specifically targets the retinal pigment epithelium, Gene Therapy online, doi:10.1038/sj.gt. 3302861.Google Scholar
  7. Lewis, G.P., Charteris, D.G., Sethi, C.S., Leitner, W.P., et al., 2002, The ability of rapid retinal reattachment to stop or reverse the cellular and molecular events initiated by detachment, Invest Ophthalmol Vis Sci, 43: 2412–2420.PubMedGoogle Scholar
  8. Narfströ m, K., Katz, M.L., Bragadottir, R., Seeliger, M., Boulanger, A., Redmoond, R.M., Caro, L., Lai, C-M., Rakoczy, P.E., 2003a, Functional and structural recovery of the retina after gene therapy in the RPE65 null mutation dog, Invest Ophthalmol Vis Sci, 44: 1663–1672.Google Scholar
  9. Narfströ m, K., Katz, M.L., Bragadottir, R., et al., 2003b, In vivo gene therapy in young and adult RPE65-/- dogs produces long-term visual improvement, J Hered, 94: 31–37.Google Scholar
  10. Narfströ m, K., Vaegan, Katz, M., Bragadottir, R., Rakoczy, E.P.,Seeliger, M., 2005, Assessment of structure and function over a 3-year period after gene transfer in RPE65-/- dog. Doc Ophthalmol, 111: 39–48.CrossRefGoogle Scholar
  11. Seeliger, M., Beck, S.C., Pereyra-Munos, N., Dangel, S., et al., 2006, In vivo confocal imaging of the retina in animals models using scanning laser ophthalmoscopy, Vis Res, 45: 3512–3519.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Kristina Narfstrô m
    • 1
  • Mathias Seeliger
  • Chooi-May Lai
    • 2
  • Vaegan
    • 3
  • Martin Katz
    • 4
  • Elizabeth P. Rakoczy
    • 5
  • Charlotte Remé
    • 6
  1. 1.Department of Veterinary Medicine and Surgery, College of Veterinary Medicine and Department of OphthalmologyMason Eye Institute, University of Missouri-ColumbiaColumbiaUSA
  2. 2.Lions Eye Institute, Centre for Ophthalmology and Visual ScienceUniversity of Western AustraliaPerthAustralia
  3. 3.School of OptometryUniversity of New South WalesAustralia
  4. 4.Mason Eye InstituteUniversity of Missouri-ColumbiaColumbiaUSA
  5. 5.Lions Eye Institute, Centre for Ophthalmology and Visual ScienceUniversity of Western AustraliaAustralia
  6. 6.Department of OphthalmologyUniversity of ZürichSwitzerland

Personalised recommendations