Journal article
Conditional deletion of Des1 in the mouse retina does not impair the visual cycle in cones
The FASEB journal, Vol.33(4), pp.5782-5792
04/01/2019
DOI: 10.1096/fj.201802493R
PMCID: PMC6436658
PMID: 30645148
Abstract
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 delta 4 desaturase 1 (Des1). Single-cell RNA sequencing analysis revealed Des1 expression not only in Muller glia but also throughout the retina and in the retinal pigment epithelium. We assessed cone functional dependence on Muller cell-expressed Des1 through a conditional knockout approach. Floxed Des1 mice, on a guanine nucleotide-binding protein subunit alpha transducin 1 knockout (Gnat1(-/-)) background to allow isolated recording of cone-driven photoresponses, were bred with platelet-derived growth factor receptor alpha (Pdgfr alpha)-Cre mice to delete Des1 in Muller 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 Muller cells is not required for cone visual pigment regeneration in the mouse.
Details
- Title: Subtitle
- Conditional deletion of Des1 in the mouse retina does not impair the visual cycle in cones
- Creators
- Philip D. Kiser - Louis Stokes Cleveland VA Medical CenterAlexander V. Kolesnikov - Washington University in St. Louis School of MedicineJianying Z. Kiser - Case Western Reserve UniversityZhiqian Dong - Polgenix (United States)Bhagirath Chaurasia - University of UtahLiping Wang - University of UtahScott A. Summers - University of UtahThanh Hoang - Johns Hopkins MedicineSeth Blackshaw - Johns Hopkins MedicineNeal S. Peachey - Cleveland ClinicVladimir J. Kefalov - Washington University in St. Louis School of MedicineKrzysztof Palczewski - Case Western Reserve University
- Resource Type
- Journal article
- Publication Details
- The FASEB journal, Vol.33(4), pp.5782-5792
- DOI
- 10.1096/fj.201802493R
- PMID
- 30645148
- PMCID
- PMC6436658
- NLM abbreviation
- FASEB J
- ISSN
- 0892-6638
- eISSN
- 1530-6860
- Publisher
- Federation Amer Soc Exp Biol
- Number of pages
- 11
- Grant note
- Research Career Scientist Award; US Department of Veterans Affairs R01EY009339; R01EY024864; R01EY019312; R01EY021126; R24EY027283; R01DK115824; P30EY011373; P30EY025585; P30EY002687 / U.S. National Institutes of Health (NIH) National Eye Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Eye Institute (NEI) R01DK115824 / NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) IK2BX002683 / U.S. Department of Veterans Affairs; US Department of Veterans Affairs American Heart Association IK2BX002683 / Veterans Affairs; US Department of Veterans Affairs R24EY024864 / NATIONAL EYE INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Eye Institute (NEI) American Diabetes Association Research to Prevent Blindness; Research to Prevent Blindness (RPB)
- Language
- English
- Date published
- 04/01/2019
- Academic Unit
- Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984359678202771
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