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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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.

Detaljer

Författare
  • Dario Marangoni
  • Zeng Yong
  • Sten Kjellström
  • Camasamudram Vijayasarathy
  • Paul A. Sieving
  • Ronald A Bush
Externa organisationer
  • National Institutes of Health, United States
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Oftalmologi

Nyckelord

Originalspråkengelska
Sidor (från-till)1656-1664
Antal sidor9
TidskriftInvestigative Ophthalmology and Visual Science
Volym58
Utgåva nummer3
StatusPublished - 2017 mar 1
PublikationskategoriForskning
Peer review utfördJa
Externt publiceradJa