Partial recovery of retinal function and structure in RPE65-/- mice and dogs following rAAV-mediated gene therapy

K. Narfstrom, M. L. Katz, R. Bragadottir, M. M. Ford, T. M. Redmond, C-M. Lai, M. J. T. Yu, M. Brankov, N. L. Barnett, S. R. Moore, C. W. Stoddart, M. T. Martin-Iverson, P. E. Rakoczy

Research output: Chapter in Book/Report/Conference proceedingChapterResearchpeer-review

Abstract

Gene transfer using a recombinant adeno-associated virus (rAAV) vector was performed in groups of Rpe65-/- knock-out mice and RPE65 null mutation dogs. Significant long-term recoveries of behavioral and electroretinographic (ERG) responses were observed in the dog model. Less substantial functional recovery occurred in the mouse model. Morphologically, in both treated species, gene therapy resulted in structural improvement in the retinal pigment epithelium (RPE). The lipid droplet accumulation, observed in RPE65 deficient animals, was reversed by RPE65 gene therapy in both species. Some reconstitution of photoreceptor outer segment structure was also observed in a dog, 10 months following gene transfer surgery. These structural improvements imply that the limited visual function obtained following gene therapy in both species occurs as a result of a restoration of the ability of the RPE to convert all-trans retinoids into 11-cis retinal.
Original languageEnglish
Title of host publicationTrends in Gene Therapy Research
EditorsG. W. Redberry
Place of PublicationNew York
PublisherNova Publishers
Chapter5
Pages129-145
Number of pages17
ISBN (Print)1-59454-306-2
Publication statusPublished - 2005

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Dependovirus
Recovery of Function
Genetic Therapy
Retinal Pigment Epithelium
Dogs
Retinaldehyde
Retinoids
Knockout Mice
Genes
Mutation

Cite this

Narfstrom, K., Katz, M. L., Bragadottir, R., Ford, M. M., Redmond, T. M., Lai, C-M., ... Rakoczy, P. E. (2005). Partial recovery of retinal function and structure in RPE65-/- mice and dogs following rAAV-mediated gene therapy. In G. W. Redberry (Ed.), Trends in Gene Therapy Research (pp. 129-145). New York: Nova Publishers.
Narfstrom, K. ; Katz, M. L. ; Bragadottir, R. ; Ford, M. M. ; Redmond, T. M. ; Lai, C-M. ; Yu, M. J. T. ; Brankov, M. ; Barnett, N. L. ; Moore, S. R. ; Stoddart, C. W. ; Martin-Iverson, M. T. ; Rakoczy, P. E. / Partial recovery of retinal function and structure in RPE65-/- mice and dogs following rAAV-mediated gene therapy. Trends in Gene Therapy Research. editor / G. W. Redberry. New York : Nova Publishers, 2005. pp. 129-145
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author = "K. Narfstrom and Katz, {M. L.} and R. Bragadottir and Ford, {M. M.} and Redmond, {T. M.} and C-M. Lai and Yu, {M. J. T.} and M. Brankov and Barnett, {N. L.} and Moore, {S. R.} and Stoddart, {C. W.} and Martin-Iverson, {M. T.} and Rakoczy, {P. E.}",
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Narfstrom, K, Katz, ML, Bragadottir, R, Ford, MM, Redmond, TM, Lai, C-M, Yu, MJT, Brankov, M, Barnett, NL, Moore, SR, Stoddart, CW, Martin-Iverson, MT & Rakoczy, PE 2005, Partial recovery of retinal function and structure in RPE65-/- mice and dogs following rAAV-mediated gene therapy. in GW Redberry (ed.), Trends in Gene Therapy Research. Nova Publishers, New York, pp. 129-145.

Partial recovery of retinal function and structure in RPE65-/- mice and dogs following rAAV-mediated gene therapy. / Narfstrom, K.; Katz, M. L.; Bragadottir, R.; Ford, M. M.; Redmond, T. M.; Lai, C-M.; Yu, M. J. T.; Brankov, M.; Barnett, N. L.; Moore, S. R.; Stoddart, C. W.; Martin-Iverson, M. T.; Rakoczy, P. E.

Trends in Gene Therapy Research. ed. / G. W. Redberry. New York : Nova Publishers, 2005. p. 129-145.

Research output: Chapter in Book/Report/Conference proceedingChapterResearchpeer-review

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Narfstrom K, Katz ML, Bragadottir R, Ford MM, Redmond TM, Lai C-M et al. Partial recovery of retinal function and structure in RPE65-/- mice and dogs following rAAV-mediated gene therapy. In Redberry GW, editor, Trends in Gene Therapy Research. New York: Nova Publishers. 2005. p. 129-145