Gene therapy restores vision in a canine model of childhood blindness
Top Cited Papers
- 1 May 2001
- journal article
- letter
- Published by Springer Nature in Nature Genetics
- Vol. 28 (1) , 92-95
- https://doi.org/10.1038/ng0501-92
Abstract
The relationship between the neurosensory photoreceptors and the adjacent retinal pigment epithelium (RPE) controls not only normal retinal function, but also the pathogenesis of hereditary retinal degenerations. The molecular bases for both primary photoreceptor1 and RPE diseases2,3,4 that cause blindness have been identified. Gene therapy has been used successfully to slow degeneration in rodent models of primary photoreceptor diseases5,6, but efficacy of gene therapy directed at photoreceptors and RPE in a large-animal model of human disease has not been reported. Here we study one of the most clinically severe retinal degenerations, Leber congenital amaurosis (LCA). LCA causes near total blindness in infancy and can result from mutations in RPE65 (LCA, type II; MIM 180069 and 204100). A naturally occurring animal model, the RPE65−/− dog, suffers from early and severe visual impairment similar to that seen in human LCA. We used a recombinant adeno-associated virus (AAV) carrying wild-type RPE65 (AAV-RPE65) to test the efficacy of gene therapy in this model. Our results indicate that visual function was restored in this large animal model of childhood blindness.Keywords
This publication has 15 references indexed in Scilit:
- Gene Therapy for Ocular DiseaseMolecular Therapy, 2000
- Rapid restoration of visual pigment and function with oral retinoid in a mouse model of childhood blindnessProceedings of the National Academy of Sciences, 2000
- [46] Genetic analysis of RPE65: From human disease to mouse modelPublished by Elsevier ,2000
- [48] Production and purification of recombinant adeno-associated virusPublished by Elsevier ,2000
- Stable transgene expression in rod photoreceptors after recombinant adeno-associated virus-mediated gene transfer to monkey retinaProceedings of the National Academy of Sciences, 1999
- Retinal Rod Photoreceptor–Specific Gene Mutation Perturbs Cone Pathway DevelopmentNeuron, 1999
- Persistent transgene product in retina, optic nerve and brain after intraocular injection of rAAVVision Research, 1999
- Rpe65 is necessary for production of 11-cis-vitamin A in the retinal visual cycleNature Genetics, 1998
- Mutations in RPE65 cause autosomal recessive childhood–onset severe retinal dystrophyNature Genetics, 1997
- Mutations in RPE65 cause Leber's congenital amaurosisNature Genetics, 1997