title: Rearing Light Intensity Affects Inner Retinal Pathology in a Mouse Model of X-Linked Retinoschisis but Does Not Alter Gene Therapy Outcome.
abstract: To test the effects of rearing light intensity on retinal function and morphology in the retinoschisis knockout (Rs1-KO) mouse model of X-linked retinoschisis, and whether it affects functional outcome of RS1 gene replacement.
  
  
  
  Seventy-six Rs1-KO mice were reared in either cyclic low light (LL, 20 lux) or moderate light (ML, 300 lux) and analyzed at 1 and 4 months. Retinal function was assessed by electroretinogram and cavity size by optical coherence tomography. Expression of inward-rectifier K+ channel (Kir4.1), water channel aquaporin-4 (AQP4), and glial fibrillary acidic protein (GFAP) were analyzed by Western blotting. In a separate study, Rs1-KO mice reared in LL (n = 29) or ML (n = 27) received a unilateral intravitreal injection of scAAV8-hRs-IRBP at 21 days, and functional outcome was evaluated at 4 months by electroretinogram.
  
  
  
  At 1 month, no functional or structural differences were found between LL- or ML-reared Rs1-KO mice. At 4 months, ML-reared Rs1-KO mice showed significant reduction of b-wave amplitude and b-/a-wave ratio with no changes in a-wave, and a significant increase in cavity size, compared to LL-reared animals. Moderate light rearing increased Kir4.1 expression in Rs1-KO mice by 4 months, but not AQP4 and GFAP levels. Administration of scAAV8-hRS1-IRBP to Rs1-KO mice showed similar improvement of inner retinal ERG function independent of LL or ML rearing.
  
  
  
  Rearing light conditions affect the development of retinal cavities and post-photoreceptor function in Rs1-KO mice. However, the effect of rearing light intensity does not interact with the efficacy of RS1 gene replacement in Rs1-KO mice.
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: Dario
authors.initials: D
authors.lastname: Marangoni
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: Zeng
authors.initials: Z
authors.lastname: Yong
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: Sten
authors.initials: S
authors.lastname: Kjellström
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: 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 2National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States.
authors.forename: Paul
authors.initials: P
authors.lastname: A 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; D015153:Blotting, Western; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D005500:Follow-Up Studies; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D008027:Light; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D024661:Potassium Channels, Inwardly Rectifying / Q000096:biosynthesis / Q000235:genetics; D012313:RNA / Q000235:genetics; D055211:Retinal Photoreceptor Cell Inner Segment / Q000473:pathology* / Q000528:radiation effects; D041441:Retinoschisis / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D013997:Time Factors; D041623:Tomography, Optical Coherence; D000098854:Kcnj10 Channel
chemical_list: D015815:Cell Adhesion Molecules; D005136:Eye Proteins; D000098854:Kcnj10 Channel; D024661:Potassium Channels, Inwardly Rectifying; C491843:RS1 protein, mouse; D012313:RNA