title: Retinal Structure and Gene Therapy Outcome in Retinoschisin-Deficient Mice Assessed by Spectral-Domain Optical Coherence Tomography.
abstract: Spectral-domain optical coherence tomography (SD-OCT) was used to characterize the retinal phenotype, natural history, and treatment responses in a mouse model of X-linked retinoschisis (Rs1-KO) and to identify new structural markers of AAV8-mediated gene therapy outcome.
  
  
  
  Optical coherence tomography scans were performed on wild-type and Rs1-KO mouse retinas between 1 and 12 months of age and on Rs1-KO mice after intravitreal injection of AAV8-scRS/IRBPhRS (AAV8-RS1). Cavities and photoreceptor outer nuclear layer (ONL) thickness were measured, and outer retina reflective band (ORRB) morphology was examined with age and after AAV8-RS1 treatment. Outer retina reflective band morphology was compared to immunohistochemical staining of the outer limiting membrane (OLM) and photoreceptor inner segment (IS) mitochondria and to electron microscopy (EM) images of IS.
  
  
  
  Retinal cavity size in Rs1-KO mice increased between 1 and 4 months and decreased thereafter, while ONL thickness declined steadily, comparable to previous histologic studies. Wild-type retina had four ORRBs. In Rs1-KO, ORRB1was fragmented from 1 month, but was normal after 8 months; ORRB2 and ORRB3 were merged at all ages. Outer retina reflective band morphology returned to normal after AAV-RS1 therapy, paralleling the recovery of the OLM and IS mitochondria as indicated by anti-β-catenin and anti-COX4 labeling, respectively, and EM.
  
  
  
  Spectral-domain OCT is a sensitive, noninvasive tool to monitor subtle changes in retinal morphology, disease progression, and effects of therapies in mouse models. The ORRBs may be useful to assess the outcome of gene therapy in the treatment of X-linked retinoschisis patients.
authors.affiliation: Section on Translational Research for Retinal and Macular Degeneration National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland, United States.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: Advanced Imaging Core, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland, United States.
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Petralia
authors.affiliation: Section on Translational Research for Retinal and Macular Degeneration National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland, United States.
authors.forename: Camasamudram
authors.initials: C
authors.lastname: Vijayasarathy
authors.affiliation: Ocular Gene Therapy Core, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States.
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Ocular Gene Therapy Core, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States.
authors.forename: Suja
authors.initials: S
authors.lastname: Hiriyanna
authors.affiliation: Section on Translational Research for Retinal and Macular Degeneration National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland, United States.
authors.forename: Hongman
authors.initials: H
authors.lastname: Song
authors.affiliation: Advanced Imaging Core, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland, United States.
authors.forename: Ya-Xian
authors.initials: YX
authors.lastname: Wang
authors.affiliation: Section on Translational Research for Retinal and Macular Degeneration National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland, United States 4National Eye Institute, National Institutes of Healt.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Sieving
authors.affiliation: Section on Translational Research for Retinal and Macular Degeneration National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland, United States.
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Bush
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000172:deficiency*; D004195:Disease Models, Animal; D004596:Electroretinography; D005136:Eye Proteins; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage*; D058449:Intravitreal Injections; D051379:Mice; D018345:Mice, Knockout; D016253:Microscopy, Immunoelectron; D012160:Retina / Q000648:ultrastructure*; D041441:Retinoschisis / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D041623:Tomography, Optical Coherence / Q000379:methods*
chemical_list: D015815:Cell Adhesion Molecules; D005136:Eye Proteins; C491843:RS1 protein, mouse