title: 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.forename: Yunlu
authors.initials: Y
authors.lastname: Xue
authors.forename: Susan Q
authors.initials: SQ
authors.lastname: Shen
authors.forename: Jonathan
authors.initials: J
authors.lastname: Jui
authors.forename: Alan C
authors.initials: AC
authors.lastname: Rupp
authors.forename: Leah C
authors.initials: LC
authors.lastname: Byrne
authors.forename: Samer
authors.initials: S
authors.lastname: Hattar
authors.forename: John G
authors.initials: JG
authors.lastname: Flannery
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Corbo
authors.forename: Vladimir J
authors.initials: VJ
authors.lastname: Kefalov
mesh_terms: D000818:Animals; D001766:Blindness / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D003623:Dark Adaptation / Q000502:physiology*; D000229:Dependovirus; D063928:Ependymoglial Cells / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D055355:Opsins / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism* / Q000473:pathology; D055213:Retinal Pigment Epithelium / Q000378:metabolism / Q000473:pathology; D014161:Transduction, Genetic; D014785:Vision, Ocular / Q000502:physiology*
chemical_list: C020932:11-cis-retinal-binding protein; D002352:Carrier Proteins; D055355:Opsins