title: Gene therapy restores vision and delays degeneration in the CNGB1(-/-) mouse model of retinitis pigmentosa.
abstract: Retinitis pigmentosa (RP) is a severe retinal disease characterized by a progressive degeneration of rod photoreceptors and a secondary loss of cone function. Here, we used CNGB1-deficient (CNGB1(-/-)) mice, a mouse model for autosomal recessive RP, to evaluate the efficacy of adeno-associated virus (AAV) vector-mediated gene therapy for the treatment of RP. The treatment restored normal expression of rod CNG channels and rod-driven light responses in the CNGB1(-/-) retina. This led to a substantial delay of retinal degeneration and long-term preservation of retinal morphology. Finally, treated CNGB1(-/-) mice performed significantly better than untreated mice in a rod-dependent vision-guided behavior test. In summary, this study holds promise for the treatment of rod channelopathy-associated retinitis pigmentosa by AAV-mediated gene replacement.
authors.affiliation: Center for Integrated Protein Science Munich (CIPSM), Department of Pharmacy-Center for Drug Research, Ludwig-Maximilians-Universität München, Butenandtstr. 5-13, 81377, Munich, Germany, michalakis@lmu.de.
authors.forename: Stylianos
authors.initials: S
authors.lastname: Michalakis
authors.forename: Susanne
authors.initials: S
authors.lastname: Koch
authors.forename: Vithiyanjali
authors.initials: V
authors.lastname: Sothilingam
authors.forename: Marina
authors.initials: M
authors.lastname: Garcia Garrido
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Tanimoto
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Schulze
authors.forename: Elvir
authors.initials: E
authors.lastname: Becirovic
authors.forename: Fred
authors.initials: F
authors.lastname: Koch
authors.forename: Christina
authors.initials: C
authors.lastname: Seide
authors.forename: Susanne C
authors.initials: SC
authors.lastname: Beck
authors.forename: Mathias W
authors.initials: MW
authors.lastname: Seeliger
authors.forename: Regine
authors.initials: R
authors.lastname: Mühlfriedel
authors.forename: Martin
authors.initials: M
authors.lastname: Biel
mesh_terms: D000818:Animals; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000235:genetics*; D000229:Dependovirus / Q000235:genetics*; D004195:Disease Models, Animal; D004596:Electroretinography; D018782:Maze Learning; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020127:Recovery of Function / Q000235:genetics*; D012162:Retinal Degeneration / Q000235:genetics / Q000628:therapy*; D017948:Retinal Rod Photoreceptor Cells / Q000502:physiology*; D012174:Retinitis Pigmentosa / Q000235:genetics / Q000628:therapy*; D014785:Vision, Ocular / Q000502:physiology
chemical_list: C529481:Cngb1 protein, mouse; D054815:Cyclic Nucleotide-Gated Cation Channels; D009419:Nerve Tissue Proteins