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Conditional deletion of Des1 in the mouse retina does not impair the visual cycle in cones

Cone photoreceptors are essential for vision under moderate to high illuminance and allow color discrimination. Their fast dark adaptation rate and resistance to saturation are believed to depend in part on an intraretinal visual cycle that supplies 11-cis-retinaldehyde to cone opsins. Candidate enz...

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Autores principales: Kiser, Philip D., Kolesnikov, Alexander V., Kiser, Jianying Z., Dong, Zhiqian, Chaurasia, Bhagirath, Wang, Liping, Summers, Scott A., Hoang, Thanh, Blackshaw, Seth, Peachey, Neal S., Kefalov, Vladimir J., Palczewski, Krzysztof
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Federation of American Societies for Experimental Biology 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6436658/
https://www.ncbi.nlm.nih.gov/pubmed/30645148
http://dx.doi.org/10.1096/fj.201802493R
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author Kiser, Philip D.
Kolesnikov, Alexander V.
Kiser, Jianying Z.
Dong, Zhiqian
Chaurasia, Bhagirath
Wang, Liping
Summers, Scott A.
Hoang, Thanh
Blackshaw, Seth
Peachey, Neal S.
Kefalov, Vladimir J.
Palczewski, Krzysztof
author_facet Kiser, Philip D.
Kolesnikov, Alexander V.
Kiser, Jianying Z.
Dong, Zhiqian
Chaurasia, Bhagirath
Wang, Liping
Summers, Scott A.
Hoang, Thanh
Blackshaw, Seth
Peachey, Neal S.
Kefalov, Vladimir J.
Palczewski, Krzysztof
author_sort Kiser, Philip D.
collection PubMed
description Cone photoreceptors are essential for vision under moderate to high illuminance and allow color discrimination. Their fast dark adaptation rate and resistance to saturation are believed to depend in part on an intraretinal visual cycle that supplies 11-cis-retinaldehyde to cone opsins. Candidate enzymes of this pathway have been reported, but their physiologic contribution to cone photoresponses remains unknown. Here, we evaluate the role of a candidate retinol isomerase of this pathway, sphingolipid δ4 desaturase 1 (Des1). Single-cell RNA sequencing analysis revealed Des1 expression not only in Müller glia but also throughout the retina and in the retinal pigment epithelium. We assessed cone functional dependence on Müller cell–expressed Des1 through a conditional knockout approach. Floxed Des1 mice, on a guanine nucleotide-binding protein subunit α transducin 1 knockout (Gnat1(−/−)) background to allow isolated recording of cone-driven photoresponses, were bred with platelet-derived growth factor receptor α (Pdgfrα)-Cre mice to delete Des1 in Müller cells. Conditional knockout of Des1 expression, as shown by tissue-selective Des1 gene recombination and reduced Des1 catalytic activity, caused no gross changes in the retinal structure and had no effect on cone sensitivity or dark adaptation but did slightly accelerate the rate of cone phototransduction termination. These results indicate that Des1 expression in Müller cells is not required for cone visual pigment regeneration in the mouse.—Kiser, P. D., Kolesnikov, A.V., Kiser, J. Z., Dong, Z., Chaurasia, B., Wang, L., Summers, S. A., Hoang, T., Blackshaw, S., Peachey, N. S., Kefalov, V. J., Palczewski, K. Conditional deletion of Des1 in the mouse retina does not impair the visual cycle in cones.
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spelling pubmed-64366582020-02-11 Conditional deletion of Des1 in the mouse retina does not impair the visual cycle in cones Kiser, Philip D. Kolesnikov, Alexander V. Kiser, Jianying Z. Dong, Zhiqian Chaurasia, Bhagirath Wang, Liping Summers, Scott A. Hoang, Thanh Blackshaw, Seth Peachey, Neal S. Kefalov, Vladimir J. Palczewski, Krzysztof FASEB J Research Cone photoreceptors are essential for vision under moderate to high illuminance and allow color discrimination. Their fast dark adaptation rate and resistance to saturation are believed to depend in part on an intraretinal visual cycle that supplies 11-cis-retinaldehyde to cone opsins. Candidate enzymes of this pathway have been reported, but their physiologic contribution to cone photoresponses remains unknown. Here, we evaluate the role of a candidate retinol isomerase of this pathway, sphingolipid δ4 desaturase 1 (Des1). Single-cell RNA sequencing analysis revealed Des1 expression not only in Müller glia but also throughout the retina and in the retinal pigment epithelium. We assessed cone functional dependence on Müller cell–expressed Des1 through a conditional knockout approach. Floxed Des1 mice, on a guanine nucleotide-binding protein subunit α transducin 1 knockout (Gnat1(−/−)) background to allow isolated recording of cone-driven photoresponses, were bred with platelet-derived growth factor receptor α (Pdgfrα)-Cre mice to delete Des1 in Müller cells. Conditional knockout of Des1 expression, as shown by tissue-selective Des1 gene recombination and reduced Des1 catalytic activity, caused no gross changes in the retinal structure and had no effect on cone sensitivity or dark adaptation but did slightly accelerate the rate of cone phototransduction termination. These results indicate that Des1 expression in Müller cells is not required for cone visual pigment regeneration in the mouse.—Kiser, P. D., Kolesnikov, A.V., Kiser, J. Z., Dong, Z., Chaurasia, B., Wang, L., Summers, S. A., Hoang, T., Blackshaw, S., Peachey, N. S., Kefalov, V. J., Palczewski, K. Conditional deletion of Des1 in the mouse retina does not impair the visual cycle in cones. Federation of American Societies for Experimental Biology 2019-04 2019-01-15 /pmc/articles/PMC6436658/ /pubmed/30645148 http://dx.doi.org/10.1096/fj.201802493R Text en © The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Kiser, Philip D.
Kolesnikov, Alexander V.
Kiser, Jianying Z.
Dong, Zhiqian
Chaurasia, Bhagirath
Wang, Liping
Summers, Scott A.
Hoang, Thanh
Blackshaw, Seth
Peachey, Neal S.
Kefalov, Vladimir J.
Palczewski, Krzysztof
Conditional deletion of Des1 in the mouse retina does not impair the visual cycle in cones
title Conditional deletion of Des1 in the mouse retina does not impair the visual cycle in cones
title_full Conditional deletion of Des1 in the mouse retina does not impair the visual cycle in cones
title_fullStr Conditional deletion of Des1 in the mouse retina does not impair the visual cycle in cones
title_full_unstemmed Conditional deletion of Des1 in the mouse retina does not impair the visual cycle in cones
title_short Conditional deletion of Des1 in the mouse retina does not impair the visual cycle in cones
title_sort conditional deletion of des1 in the mouse retina does not impair the visual cycle in cones
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6436658/
https://www.ncbi.nlm.nih.gov/pubmed/30645148
http://dx.doi.org/10.1096/fj.201802493R
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