CRALBP Supports the Mammalian Retinal Visual Cycle and Cone Vision

Overview

Journal J Clin Invest

Specialty General Medicine

Date 2015 Jan 22

PMID 25607845

Citations 72

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

Affiliations

Soon will be listed here.

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.

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