Rearing light intensity affects inner retinal pathology in a mouse model of x-linked retinoschisis but does not alter gene therapy outcome

Dario Marangoni, Zeng Yong, Sten Kjellström, Camasamudram Vijayasarathy, Paul A. Sieving, Ronald A. Bush

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

PURPOSE. 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. METHODS. 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. RESULTS. 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. CONCLUSIONS. 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.

Original languageEnglish (US)
Pages (from-to)1656-1664
Number of pages9
JournalInvestigative Ophthalmology and Visual Science
Volume58
Issue number3
DOIs
StatePublished - Mar 2017
Externally publishedYes

Keywords

  • Electroretinogram
  • Gene therapy
  • OCT
  • Rearing light
  • Rs1-KO mouse

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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