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Partial Recovery of Retinal Function and Structure in RPE65-/- Mice and Dogs Following rAAV-Mediated Gene Therapy pp. 129-145 $25.00
Authors:  Narfstr÷ma, M.L. Katzb, R. Bragadˇttirc, M.M. Forda, T.M. Redmondd, C.-M. Laie, M.J.T. Yue,f, M. Brankove, N.L. Barnettf,g, S.R.Mooree,f, C.W. Stoddarth, M.T. Martin-Iversonh and P.E. Rakoczye
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. 


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Partial Recovery of Retinal Function and Structure in RPE65-/- Mice and Dogs Following rAAV-Mediated Gene Therapy pp. 129-145