Cone photoreceptors mediate daytime vision in vertebrates. The rapid and efficient regeneration of their visual pigments following photoactivation is critical for the cones to remain photoresponsive in bright and rapidly changing light conditions. Cone pigment regeneration depends on the recycling of visual chromophore, which takes place via the canonical visual cycle in the retinal pigment epithelium (RPE) and the Müller cell–driven intraretinal visual cycle. The molecular mechanisms that enable the neural retina to regenerate visual chromophore for cones have not been fully elucidated. However, one known component of the two visual cycles is the cellular retinaldehyde-binding protein (CRALBP), which is expressed both in the RPE and in Müller cells. To understand the significance of CRALBP in cone pigment regeneration, we examined the function of cones in mice heterozygous for Rlbp1, the gene encoding CRALBP. We found that CRALBP expression was reduced by ∼50% in both the RPE and retina of Rlbp1+/− mice. Electroretinography (ERG) showed that the dark adaptation of rods and cones is unaltered in Rlbp1+/− mice, indicating a normal RPE visual cycle. However, pharmacologic blockade of the RPE visual cycle revealed suppressed cone dark adaptation in Rlbp1+/− mice in comparison with controls. We conclude that the expression level of CRALPB specifically in the Müller cells modulates the efficiency of the retina visual cycle. Finally, blocking the RPE visual cycle also suppressed further cone dark adaptation in Rlbp1−/− mice, revealing a shunt in the classical RPE visual cycle that bypasses CRALBP and allows partial but unexpectedly rapid cone dark adaptation.
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4 January 2021
Article|
November 20 2020
Function of mammalian M-cones depends on the level of CRALBP in Müller cells
Alexander V. Kolesnikov,
Alexander V. Kolesnikov
1
Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO
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Philip D. Kiser,
Philip D. Kiser
2
Department of Physiology and Biophysics, School of Medicine, University of California, Irvine, Irvine, CA
3
Department of Ophthalmology, Gavin Herbert Eye Institute, Center for Translation Vision Research, School of Medicine, University of California, Irvine, Irvine, CA
4
Research Service, VA Long Beach Healthcare System, Long Beach, CA
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Krzysztof Palczewski,
Krzysztof Palczewski
2
Department of Physiology and Biophysics, School of Medicine, University of California, Irvine, Irvine, CA
3
Department of Ophthalmology, Gavin Herbert Eye Institute, Center for Translation Vision Research, School of Medicine, University of California, Irvine, Irvine, CA
5
Department of Chemistry, School of Medicine, University of California, Irvine, Irvine, CA
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Vladimir J. Kefalov
1
Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO
Correspondence to Vladimir J. Kefalov: kefalov@wustl.edu
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Alexander V. Kolesnikov
1
Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO
Philip D. Kiser
2
Department of Physiology and Biophysics, School of Medicine, University of California, Irvine, Irvine, CA
3
Department of Ophthalmology, Gavin Herbert Eye Institute, Center for Translation Vision Research, School of Medicine, University of California, Irvine, Irvine, CA
4
Research Service, VA Long Beach Healthcare System, Long Beach, CA
Krzysztof Palczewski
2
Department of Physiology and Biophysics, School of Medicine, University of California, Irvine, Irvine, CA
3
Department of Ophthalmology, Gavin Herbert Eye Institute, Center for Translation Vision Research, School of Medicine, University of California, Irvine, Irvine, CA
5
Department of Chemistry, School of Medicine, University of California, Irvine, Irvine, CA
Vladimir J. Kefalov
1
Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO
Correspondence to Vladimir J. Kefalov: kefalov@wustl.edu
Received:
June 10 2020
Revision Received:
September 16 2020
Accepted:
October 27 2020
Online Issn: 1540-7748
Print Issn: 0022-1295
Funding:
National Institutes of Health
(EY027283, EY009339, EY002687)
Research to Prevent Blindness
(NO AWARD)
U.S. Department of Veterans Affairs
(I01BX004939)
© 2020 Kolesnikov et al.
2020
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
J Gen Physiol (2021) 153 (1): e202012675.
Article history
Received:
June 10 2020
Revision Received:
September 16 2020
Accepted:
October 27 2020
Citation
Alexander V. Kolesnikov, Philip D. Kiser, Krzysztof Palczewski, Vladimir J. Kefalov; Function of mammalian M-cones depends on the level of CRALBP in Müller cells. J Gen Physiol 4 January 2021; 153 (1): e202012675. doi: https://doi.org/10.1085/jgp.202012675
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