Rearing light intensity affects inner retinal pathology in a mouse model of x-linked retinoschisis but does not alter gene therapy outcome
(2017) In Investigative Ophthalmology and Visual Science 58(3). p.1656-1664- 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... (More)
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.
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- author
- Marangoni, Dario ; Yong, Zeng ; Kjellström, Sten LU ; Vijayasarathy, Camasamudram ; Sieving, Paul A. and Bush, Ronald A
- publishing date
- 2017-03-01
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Electroretinogram, Gene therapy, OCT, Rearing light, Rs1-KO mouse
- in
- Investigative Ophthalmology and Visual Science
- volume
- 58
- issue
- 3
- pages
- 9 pages
- publisher
- Association for Research in Vision and Ophthalmology Inc.
- external identifiers
-
- scopus:85015319990
- pmid:28297725
- ISSN
- 0146-0404
- DOI
- 10.1167/iovs.16-21016
- language
- English
- LU publication?
- no
- id
- dc663ec3-4289-4d5f-842f-3e3450db668a
- date added to LUP
- 2017-04-11 16:02:39
- date last changed
- 2024-03-17 12:02:08
@article{dc663ec3-4289-4d5f-842f-3e3450db668a,
abstract = {{<p>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<sup>+</sup> 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.</p>}},
author = {{Marangoni, Dario and Yong, Zeng and Kjellström, Sten and Vijayasarathy, Camasamudram and Sieving, Paul A. and Bush, Ronald A}},
issn = {{0146-0404}},
keywords = {{Electroretinogram; Gene therapy; OCT; Rearing light; Rs1-KO mouse}},
language = {{eng}},
month = {{03}},
number = {{3}},
pages = {{1656--1664}},
publisher = {{Association for Research in Vision and Ophthalmology Inc.}},
series = {{Investigative Ophthalmology and Visual Science}},
title = {{Rearing light intensity affects inner retinal pathology in a mouse model of x-linked retinoschisis but does not alter gene therapy outcome}},
url = {{http://dx.doi.org/10.1167/iovs.16-21016}},
doi = {{10.1167/iovs.16-21016}},
volume = {{58}},
year = {{2017}},
}