AAV-mediated intravitreal gene therapy reduces lysosomal storage in the retinal pigmented epithelium and improves retinal function in adult MPS VII mice

Molecular Therapy : the Journal of the American Society of Gene Therapy
Anne K HennigMark S Sands

Abstract

The beta-glucuronidase-deficient mucopolysaccharidosis type VII (MPS VII) mouse accumulates partially degraded glycosaminoglycans in many cell types, including retinal pigmented epithelial (RPE) cells in the eye. This lysosomal storage in RPE cells leads to progressive retinal degeneration and reduced function as measured by flash electroretinography (ERG). The impact of AAV-mediated intraocular gene therapy on pathology and retinal function was examined in normal and MPS VII mice treated at 4 weeks of age, when lysosomal storage is evident but functional impairment is minimal in affected animals. At 16 weeks, an age at which untreated MPS VII mice have advanced histologic lesions and significantly reduced ERG amplitudes, treated eyes had nearly normal levels of beta-glucuronidase activity, preservation of cells in the outer nuclear layer of the retina, and decreased lysosomal storage within the RPE. The AAV-treated MPS VII mice also had significantly increased dark-adapted ERG amplitudes compared to untreated MPS VII mice. Although retinal function was improved, the efficacy of the treatment depended heavily on parameters related to the injection procedure, such as the injection volume, injection site, and vector dose. These d...Continue Reading

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Citations

Aug 19, 2007·Journal of Virology·Mariacarmela AlloccaAlberto Auricchio
Oct 22, 2009·Molecular Therapy : the Journal of the American Society of Gene Therapy·Jason A MetcalfKatherine P Ponder
Jan 17, 2007·Expert Opinion on Biological Therapy·Mariacarmela AlloccaAlberto Auricchio
Aug 31, 2007·Expert Opinion on Biological Therapy·Katherine P Ponder, Mark E Haskins
Oct 4, 2005·Expert Opinion on Biological Therapy·Ian ConstableElizabeth Rakoczy
Jul 10, 2008·The Journal of Gene Medicine·Ramin Sedaghat HeratiKatherine P Ponder
Oct 10, 2007·Vision Research·Enrico M Surace, Alberto Auricchio
Jun 28, 2005·Molecular Therapy : the Journal of the American Society of Gene Therapy·Megan GriffeyMark S Sands
Dec 9, 2004·Molecular Therapy : the Journal of the American Society of Gene Therapy·Yuli LiuKatherine Parker Ponder
Mar 21, 2006·Molecular Therapy : the Journal of the American Society of Gene Therapy·Mark S Sands, Beverly L Davidson
Feb 22, 2007·Molecular Therapy : the Journal of the American Society of Gene Therapy·Xiucui MaKatherine P Ponder
Apr 29, 2006·Molecular Therapy : the Journal of the American Society of Gene Therapy·Samuel G JacobsonWilliam W Hauswirth
Jan 20, 2007·Molecular Therapy : the Journal of the American Society of Gene Therapy·Gumei LiuBeverly L Davidson
Apr 11, 2008·Gene Therapy·I E AlexanderJ Christodoulou
Jul 14, 2006·Gene Therapy·J W B BainbridgeR R Ali
Jul 1, 2017·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Adeline A Lau, Kim M Hemsley
Mar 1, 2021·The American Journal of Pathology·Rubens P HommeMahavir Singh
May 17, 2021·The FEBS Journal·Daniela IntartagliaIvan Conte

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