biostudies-literatureSong JYBrenda and Matthew Shapiro StewardshipNEI NIH HHSResearch to Prevent BlindnessCore Grant for Vision ResearchPaul and Evanina Mackall Foundation TrustFoundation Fighting BlindnessRobert and Susan Heidenberg Investigative Research Fund for Ocular Gene TherapyF.M. Kirby FoundationFFB-CanadaCenter for Advanced Retinal and Ocular TherapeuticsNational Eye Institute/NIHCIHR1581-1593https://www.ebi.ac.uk/biostudies/studies/S-EPMC5986734biostudies-literatureUnknown26(6)Most genetically distinct inherited retinal degenerations are primary photoreceptor degenerations. We selected a severe early onset form of Leber congenital amaurosis (LCA), caused by mutations in the gene LCA5, in order to test the efficacy of gene augmentation therapy for a ciliopathy. The LCA5-encoded protein, Lebercilin, is essential for the trafficking of proteins and vesicles to the photoreceptor outer segment. Using the AAV serotype AAV7m8 to deliver a human LCA5 cDNA into an Lca5 null mouse model of LCA5, we show partial rescue of retinal structure and visual function. Specifically, we observed restoration of rod-and-cone-driven electroretinograms in about 25% of injected eyes, restoration of pupillary light responses in the majority of treated eyes, an ∼20-fold decrease in target Molecular therapy : the journal of the American Society of Gene TherapyAmelioration of Neurosensory Structure and Function in Animal and Cellular Models of a Congenital Blindness.PMC5986734P30 EY0015838DP1EY023177R24 EY0198611R24 EY019861-01A1DP1 EY023177Aleman TSCremers FPMPham Jden Hollander AIMcNamara INishina PAravand PBennett DJWei ZSong JYLyubarsky ASun JPan Wde Melo JZhou SMaguire AMRoepman RHerrera PBennett JMills JPan JShpylchak INikonov SYing GSBennicelli JLLeo LKoenekoop RKCommins NfalseAmelioration of Neurosensory Structure and Function in Animal and Cellular Models of a Congenital Blindness.Most genetically distinct inherited retinal degenerations are primary photoreceptor degenerations. We selected a severe early onset form of Leber congenital amaurosis (LCA), caused by mutations in the gene LCA5, in order to test the efficacy of gene augmentation therapy for a ciliopathy. The LCA5-encoded protein, Lebercilin, is essential for the trafficking of proteins and vesicles to the photoreceptor outer segment. Using the AAV serotype AAV7m8 to deliver a human LCA5 cDNA into an Lca5 null mouse model of LCA5, we show partial rescue of retinal structure and visual function. Specifically, we observed restoration of rod-and-cone-driven electroretinograms in about 25% of injected eyes, restoration of pupillary light responses in the majority of treated eyes, an ∼20-fold decrease in target 2018-01-01T00:00:00Z2018 Jun2026-05-03T11:57:59.084Z2019-07-24T07:13:17ZS-EPMC59867342967393010.1016/j.ymthe.2018.03.015