Dominant role for pigment epithelial CRALBP in supplying visual chromophore to photoreceptors. 2024

Marco Bassetto, and Alexander V Kolesnikov, and Dominik Lewandowski, and Jianying Z Kiser, and Maximilian Halabi, and David E Einstein, and Elliot H Choi, and Krzysztof Palczewski, and Vladimir J Kefalov, and Philip D Kiser
Department of Physiology & Biophysics, University of California Irvine, Irvine, CA 92697, USA; Research Service, Tibor Rubin VA Long Beach Medical Center, Long Beach, CA 90822, USA; Center for Translational Vision Research, Gavin Herbert Eye Institute, Department of Ophthalmology, University of California Irvine, Irvine, CA 92697, USA.

Cellular retinaldehyde-binding protein (CRALBP) supports production of 11-cis-retinaldehyde and its delivery to photoreceptors. It is found in the retinal pigment epithelium (RPE) and Müller glia (MG), but the relative functional importance of these two cellular pools is debated. Here, we report RPE- and MG-specific CRALBP knockout (KO) mice and examine their photoreceptor and visual cycle function. Bulk visual chromophore regeneration in RPE-KO mice is 15-fold slower than in controls, accounting for their delayed rod dark adaptation and protection against retinal phototoxicity, whereas MG-KO mice have normal bulk visual chromophore regeneration and retinal light damage susceptibility. Cone pigment regeneration is significantly impaired in RPE-KO mice but mildly affected in MG-KO mice, disclosing an unexpectedly strong reliance of cone photoreceptors on the RPE-based visual cycle. These data reveal a dominant role for RPE-CRALBP in supporting rod and cone function and highlight the importance of RPE cell targeting for CRALBP gene therapies.

UI MeSH Term Description Entries
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D002352 Carrier Proteins Proteins that bind or transport specific substances in the blood, within the cell, or across cell membranes. Binding Proteins,Carrier Protein,Transport Protein,Transport Proteins,Binding Protein,Protein, Carrier,Proteins, Carrier
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012168 Retinal Pigments Photosensitive protein complexes of varied light absorption properties which are expressed in the PHOTORECEPTOR CELLS. They are OPSINS conjugated with VITAMIN A-based chromophores. Chromophores capture photons of light, leading to the activation of opsins and a biochemical cascade that ultimately excites the photoreceptor cells. Retinal Photoreceptor Pigment,Retinal Pigment,Visual Pigment,Visual Pigments,Retinal Photoreceptor Pigments,Photoreceptor Pigment, Retinal,Photoreceptor Pigments, Retinal,Pigment, Retinal,Pigment, Retinal Photoreceptor,Pigment, Visual,Pigments, Retinal,Pigments, Retinal Photoreceptor,Pigments, Visual
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D055213 Retinal Pigment Epithelium The single layer of pigment-containing epithelial cells in the RETINA, situated closely to the tips (outer segments) of the RETINAL PHOTORECEPTOR CELLS. These epithelial cells are macroglia that perform essential functions for the photoreceptor cells, such as in nutrient transport, phagocytosis of the shed photoreceptor membranes, and ensuring retinal attachment. Epithelium, Retinal Pigment,Pigment Epithelium, Retinal
D017948 Retinal Rod Photoreceptor Cells Photosensitive afferent neurons located in the peripheral retina, with their density increases radially away from the FOVEA CENTRALIS. Being much more sensitive to light than the RETINAL CONE CELLS, the rod cells are responsible for twilight vision (at scotopic intensities) as well as peripheral vision, but provide no color discrimination. Photoreceptors, Rod,Retinal Rod Cells,Rod Photoreceptors,Rods (Retina),Retinal Rod,Retinal Rod Cell,Retinal Rod Photoreceptor,Retinal Rod Photoreceptors,Rod Photoreceptor Cells,Cell, Retinal Rod,Cell, Rod Photoreceptor,Cells, Retinal Rod,Cells, Rod Photoreceptor,Photoreceptor Cell, Rod,Photoreceptor Cells, Rod,Photoreceptor, Retinal Rod,Photoreceptor, Rod,Photoreceptors, Retinal Rod,Retinal Rods,Rod (Retina),Rod Cell, Retinal,Rod Cells, Retinal,Rod Photoreceptor,Rod Photoreceptor Cell,Rod Photoreceptor, Retinal,Rod Photoreceptors, Retinal,Rod, Retinal,Rods, Retinal
D017949 Retinal Cone Photoreceptor Cells Photosensitive afferent neurons located primarily within the FOVEA CENTRALIS of the MACULA LUTEA. There are three major types of cone cells (red, blue, and green) whose photopigments have different spectral sensitivity curves. Retinal cone cells operate in daylight vision (at photopic intensities) providing color recognition and central visual acuity. Cone Photoreceptors,Cones (Retina),Cone Photoreceptor Cells,Photoreceptors, Cone,Retinal Cone,Retinal Cone Cells,Retinal Cone Photoreceptors,Cell, Cone Photoreceptor,Cell, Retinal Cone,Cells, Cone Photoreceptor,Cells, Retinal Cone,Cone (Retina),Cone Cell, Retinal,Cone Cells, Retinal,Cone Photoreceptor,Cone Photoreceptor Cell,Cone Photoreceptor, Retinal,Cone Photoreceptors, Retinal,Cone, Retinal,Cones, Retinal,Photoreceptor Cell, Cone,Photoreceptor Cells, Cone,Photoreceptor, Cone,Photoreceptor, Retinal Cone,Photoreceptors, Retinal Cone,Retinal Cone Cell,Retinal Cone Photoreceptor,Retinal Cones
D018345 Mice, Knockout Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes. Knockout Mice,Mice, Knock-out,Mouse, Knockout,Knock-out Mice,Knockout Mouse,Mice, Knock out
D063928 Ependymoglial Cells The macroglial cells of EPENDYMA. They are characterized by bipolar cell body shape and processes that contact BASAL LAMINA around blood vessels and/or the PIA MATER and the CEREBRAL VENTRICLES. Muller cells of the RETINA are included based on similar microenvironmental contacts and morphology. Ependymoglial Cell,Muller Cell,Muller Glia Cells,Muller Glial Cells,Radial Glia,Radial Glial Cell,Retinal Muller Cell,Retinal Muller Glial Cells,Tanycyte,Muller Cells,Radial Glial Cells,Retinal Muller Cells,Tanycytes,Cell, Ependymoglial,Cell, Muller,Cell, Radial Glial,Cell, Retinal Muller,Cells, Ependymoglial,Cells, Muller,Cells, Muller Glia,Cells, Muller Glial,Cells, Radial Glial,Cells, Retinal Muller,Glia Cells, Muller,Glia, Radial,Glial Cell, Radial,Glial Cells, Muller,Glial Cells, Radial,Glias, Radial,Muller Cell, Retinal,Muller Cells, Retinal,Radial Glias

Related Publications

Marco Bassetto, and Alexander V Kolesnikov, and Dominik Lewandowski, and Jianying Z Kiser, and Maximilian Halabi, and David E Einstein, and Elliot H Choi, and Krzysztof Palczewski, and Vladimir J Kefalov, and Philip D Kiser
February 2003, Experimental eye research,
Marco Bassetto, and Alexander V Kolesnikov, and Dominik Lewandowski, and Jianying Z Kiser, and Maximilian Halabi, and David E Einstein, and Elliot H Choi, and Krzysztof Palczewski, and Vladimir J Kefalov, and Philip D Kiser
January 1982, Israel journal of medical sciences,
Marco Bassetto, and Alexander V Kolesnikov, and Dominik Lewandowski, and Jianying Z Kiser, and Maximilian Halabi, and David E Einstein, and Elliot H Choi, and Krzysztof Palczewski, and Vladimir J Kefalov, and Philip D Kiser
April 2006, The Journal of biological chemistry,
Marco Bassetto, and Alexander V Kolesnikov, and Dominik Lewandowski, and Jianying Z Kiser, and Maximilian Halabi, and David E Einstein, and Elliot H Choi, and Krzysztof Palczewski, and Vladimir J Kefalov, and Philip D Kiser
May 1989, Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme,
Marco Bassetto, and Alexander V Kolesnikov, and Dominik Lewandowski, and Jianying Z Kiser, and Maximilian Halabi, and David E Einstein, and Elliot H Choi, and Krzysztof Palczewski, and Vladimir J Kefalov, and Philip D Kiser
February 1988, Experimental eye research,
Marco Bassetto, and Alexander V Kolesnikov, and Dominik Lewandowski, and Jianying Z Kiser, and Maximilian Halabi, and David E Einstein, and Elliot H Choi, and Krzysztof Palczewski, and Vladimir J Kefalov, and Philip D Kiser
January 1984, Vision research,
Marco Bassetto, and Alexander V Kolesnikov, and Dominik Lewandowski, and Jianying Z Kiser, and Maximilian Halabi, and David E Einstein, and Elliot H Choi, and Krzysztof Palczewski, and Vladimir J Kefalov, and Philip D Kiser
March 2005, The Journal of biological chemistry,
Marco Bassetto, and Alexander V Kolesnikov, and Dominik Lewandowski, and Jianying Z Kiser, and Maximilian Halabi, and David E Einstein, and Elliot H Choi, and Krzysztof Palczewski, and Vladimir J Kefalov, and Philip D Kiser
November 2001, Neuron,
Marco Bassetto, and Alexander V Kolesnikov, and Dominik Lewandowski, and Jianying Z Kiser, and Maximilian Halabi, and David E Einstein, and Elliot H Choi, and Krzysztof Palczewski, and Vladimir J Kefalov, and Philip D Kiser
January 2009, Visual neuroscience,
Marco Bassetto, and Alexander V Kolesnikov, and Dominik Lewandowski, and Jianying Z Kiser, and Maximilian Halabi, and David E Einstein, and Elliot H Choi, and Krzysztof Palczewski, and Vladimir J Kefalov, and Philip D Kiser
April 1983, Physiological reviews,
Copied contents to your clipboard!