CRALBP supports the mammalian retinal visual cycle and cone vision
Yunlu Xue, … , Joseph C. Corbo, Vladimir J. Kefalov
Yunlu Xue, … , Joseph C. Corbo, Vladimir J. Kefalov
Published January 20, 2015
Citation Information: J Clin Invest. 2015;125(2):727-738. https://doi.org/10.1172/JCI79651.
View: Text | PDF
Research Article Ophthalmology

CRALBP supports the mammalian retinal visual cycle and cone vision

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 Müller cells, but not retinal pigment epithelial (RPE) cells, rescued the retinal visual cycle and M-cone sensitivity in knockout mice. Our results identify Müller 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.

Authors

Yunlu Xue, Susan Q. Shen, Jonathan Jui, Alan C. Rupp, Leah C. Byrne, Samer Hattar, John G. Flannery, Joseph C. Corbo, Vladimir J. Kefalov

×

Figure 5

Deletion of CRALBP affects the localization of M-opsin and number of cones expressing M-opsin.

Options: View larger image (or click on image) Download as PowerPoint
Deletion of CRALBP affects the localization of M-opsin and number of con...
Antibody staining of retinal frozen sections from Rlbp1–/– and control mice for (A) M-opsin and (B) S-opsin. Representative images are shown. At least 3 retinae per condition were examined. Scale bars: 25 μm. COS, cone outer segment; ONL, outer nuclear layer; OPL, outer plexiform layer. For clarity, the DAPI channel is not shown. (C) Quantification of whole-mount M-opsin antibody staining (n = 4 retinae per condition). *P < 0.05, **P < 0.01 by unpaired 2-tailed Student’s t test. (D) Quantification of whole-mount S-opsin antibody staining (n = 3 retinae per condition). D, dorsal; T, temporal; N, nasal; V, ventral. Young, 6- to 7-week-old mice; Old, 3- to 6-month-old mice. Results represent the mean ± SEM.