Journal article
CRALBP supports the mammalian retinal visual cycle and cone vision
The Journal of clinical investigation, Vol.125(2), pp.727-738
02/01/2015
DOI: 10.1172/JCI79651
PMCID: PMC4319437
PMID: 25607845
Abstract
Mutations in the cellular retinaldehyde-binding protein (CRALBP, encoded by RLBP1) can lead to severe cone photoreceptor-mediated vision loss in patients. It is not known how CRALBP supports cone function or how altered CRALBP leads to cone dysfunction. Here, we determined that deletion of Rlbp1 in mice impairs the retinal visual cycle. Mice lacking CRALBP exhibited M-opsin mislocalization, M-cone loss, and impaired cone-driven visual behavior and light responses. Additionally, M-cone dark adaptation was largely suppressed in CRALBP-deficient animals. While rearing CRALBP-deficient mice in the dark prevented the deterioration of cone function, it did not rescue cone dark adaptation. Adeno-associated virus-mediated restoration of CRALBP expression specifically in Muller cells, but not retinal pigment epithelial (RPE) cells, rescued the retinal visual cycle and M-cone sensitivity in knockout mice. Our results identify Muller cell CRALBP as a key component of the retinal visual cycle and demonstrate that this pathway is important for maintaining normal cone-driven vision and accelerating cone dark adaptation.
Details
- Title: Subtitle
- CRALBP supports the mammalian retinal visual cycle and cone vision
- Creators
- Yunlu Xue - Washington Univ, Sch Med, Dept Ophthalmol & Visual Sci, St Louis, MO 63110 USASusan Q. Shen - Washington University in St. LouisJonathan Jui - University of California, BerkeleyAlan C. Rupp - Johns Hopkins UniversityLeah C. Byrne - University of California, BerkeleySamer Hattar - Johns Hopkins UniversityJohn G. Flannery - University of California, BerkeleyJoseph C. Corbo - Washington University in St. LouisVladimir J. Kefalov - Washington Univ, Sch Med, Dept Ophthalmol & Visual Sci, St Louis, MO 63110 USA
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.125(2), pp.727-738
- Publisher
- Amer Soc Clinical Investigation Inc
- DOI
- 10.1172/JCI79651
- PMID
- 25607845
- PMCID
- PMC4319437
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Number of pages
- 12
- Grant note
- Human Frontier Science Program Foundation Fighting Blindness EY019312; EY021126; EY18826; HG006790; HG006346; GM076430-09; 5T32EY013360-15; EY002687 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Research to Prevent Blindness; Research to Prevent Blindness (RPB)
- Language
- English
- Date published
- 02/01/2015
- Academic Unit
- Psychiatry; Iowa Neuroscience Institute
- Record Identifier
- 9984618643702771
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