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Type: Journal article
Title: Phenotypic rescue after adeno-associated virus-mediated delivery of 4-sulfatase to the retinal pigment epithelium of feline mucopolysaccharidosis VI
Author: Ho, T.
Maguire, A.
Aguirre, G.
Surace, E.
Anand, V.
Zeng, Y.
Salvetti, A.
Hopwood, J.
Haskins, M.
Bennett, J.
Citation: Journal of Gene Medicine, 2002; 4(6):613-621
Publisher: John Wiley & Sons Ltd
Issue Date: 2002
ISSN: 1099-498X
Statement of
Thucanh T. Ho, Albert M. Maguire, Gustavo D. Aguirre, Enrico M. Surace, Vibha Anand, Yong Zeng, Anna Salvetti, John J. Hopwood, Mark E. Haskins, Jean Bennett
Abstract: BACKGROUND: Mucopolysaccharidosis VI (MPS VI), due to recessively inherited 4-sulfatase (4S) deficiency, results in lysosomal storage of dermatan sulfate in numerous tissues. Retinal involvement is limited to the retinal pigment epithelium (RPE). This study aimed to determine whether recombinant adeno-associated virus (AAV)-mediated delivery of 4S would reverse the RPE pathology seen in MPS VI cats. METHODS: AAV.f4S, containing the feline 4S cDNA, was delivered unilaterally to eyes of affected cats by subretinal or intravitreal injection. Contralateral eyes received AAV with the green fluorescent protein (GFP) reporter gene as control. At 2-11 months post-injection, the cats were sacrificed and the treatment effects were evaluated histologically. RESULTS: By ophthalmoscopy and histological analyses, GFP was evident as early as 4 weeks and persisted through the latest time point (11 months). Untreated and AAV.GFP-treated diseased retinas contained massively hypertrophied RPE cells secondary to accumulation of dilated lysosomal inclusions containing dermatan sulfate. MPS VI eyes treated subretinally with AAV.f4S had minimal RPE cell inclusions and, consequently, were not hypertrophied. CONCLUSIONS: AAV-mediated subretinal delivery of f4S provided correction of the disease phenotype in RPE cells of feline MPS VI, supporting the utility of AAV as a vector for the treatment of RPE-specific as well as lysosomal storage diseases.
Keywords: Pigment Epithelium of Eye; Animals; Cats; Dependovirus; Mucopolysaccharidosis VI; Sulfatases; Luminescent Proteins; Green Fluorescent Proteins; In Situ Hybridization; Antibody Formation; Recombination, Genetic; Phenotype; Genetic Therapy
RMID: 0020021116
DOI: 10.1002/jgm.302
Appears in Collections:Paediatrics publications

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