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. Copyright 2002 John Wiley & Sons, Ltd.
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 VIcats. 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. Copyright 2002 John Wiley & Sons, Ltd.
Authors: Allison M Bradbury; Brittney L Gurda; Margret L Casal; Katherine P Ponder; Charles H Vite; Mark E Haskins Journal: Hum Gene Ther Clin Dev Date: 2015-02-11 Impact factor: 5.032
Authors: Margaret Z Jones; Joseph Alroy; Erinn Downs-Kelly; Rebecca E Lucas; Stacey A Kraemer; Kevin T Cavanagh; Barbara King; John J Hopwood Journal: J Mol Neurosci Date: 2004 Impact factor: 3.444
Authors: A L Minella; F M Mowat; K L Willett; D Sledge; J T Bartoe; J Bennett; S M Petersen-Jones Journal: Gene Ther Date: 2014-07-24 Impact factor: 5.250
Authors: Mariacarmela Allocca; Claudio Mussolino; Maria Garcia-Hoyos; Daniela Sanges; Carolina Iodice; Marco Petrillo; Luk H Vandenberghe; James M Wilson; Valeria Marigo; Enrico M Surace; Alberto Auricchio Journal: J Virol Date: 2007-08-15 Impact factor: 5.103