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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.
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Research Article Ophthalmology Article has an altmetric score of 7

CRALBP supports the mammalian retinal visual cycle and cone vision

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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

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Figure 2

Deletion of CRALBP reduces transretinal cone-response amplitude and sensitivity.

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Deletion of CRALBP reduces transretinal cone-response amplitude and sens...
(A) Representative transretinal cone responses from control (left panel) and Rlbp1–/– (right panel) retinae. Test flash intensities increased from 23 photons/μm2 to 1.40 × 106 photons/μm2 in steps of 0.5 log units. For both panels, the flash intensity producing the response shown in red was 1.39 × 104 photons/μm2. (B) Ensemble-averaged absolute and normalized (inset) cone intensity-response curves for control (n = 13) and Rlbp1–/– (n = 13) retinae. (C) Ensemble-averaged normalized cone dim flash responses from control (n = 12) and Rlbp1–/– (n = 13) retinae. (D) Ensemble-averaged dim flash responses, r, from control (n = 13) and Rlbp1–/– (n = 11) cones normalized to the maximal response, rmax, and to flash intensity and with matched rising slopes to determine the change in phototransduction amplification. Results are shown as the mean ± SEM.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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