July 2019
Volume 60, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2019
Conditional deletion of Des1 in the mouse retina does not impair the visual cycle in cones
Author Affiliations & Notes
  • Philip Kiser
    Physiology and Biophysics, University of California Irvine, Irvine, California, United States
    Research, Louis Stokes Cleveland VAMC, Cleveland, Ohio, United States
  • Alexander V Kolesnikov
    Washington University, Missouri, United States
  • Jianying Kiser
    Ophthalmology, University of California Irvine, Irvine, California, United States
  • Zhiqian Dong
    Polgenix Inc., California, United States
  • Bhagirath Chaurasia
    University of Utah, Utah, United States
  • Liping Wang
    University of Utah, Utah, United States
  • Scott Summers
    University of Utah, Utah, United States
  • Thanh Hoang
    Johns Hopkins University, Maryland, United States
  • Seth Blackshaw
    Johns Hopkins University, Maryland, United States
  • Neal S Peachey
    Research, Louis Stokes Cleveland VAMC, Cleveland, Ohio, United States
  • Vladimir Kefalov
    Washington University, Missouri, United States
  • Krzysztof Palczewski
    Ophthalmology, University of California Irvine, Irvine, California, United States
  • Footnotes
    Commercial Relationships   Philip Kiser, None; Alexander Kolesnikov, None; Jianying Kiser, None; Zhiqian Dong, None; Bhagirath Chaurasia, None; Liping Wang, None; Scott Summers, None; Thanh Hoang, None; Seth Blackshaw, None; Neal Peachey, None; Vladimir Kefalov, None; Krzysztof Palczewski, None
  • Footnotes
    Support  Department of Veterans Affairs: IK2BX002683 (P.D.K.) and a Research Career Scientist Award (N.S.P.); the National Institutes of Health: R01EY009339 (K.P. and P.D.K.), R01EY024864 (K.P.), R01EY019312 (V.J.K.), R01EY021126 (K.P. and V.J.K.), R24EY027283 (K.P., P.D.K., V.J.K., S.B., N.S.P.), R01DK115824 (S.A.S.) and P30EY011373 to the Department of Ophthalmology and Visual Sciences at Case Western Reserve University, P30EY025585 to the Cleveland Clinic Cole Eye Institute and P30EY002687 to the Department of Ophthalmology and Visual Sciences at Washington University; the American Diabetes Association (S.A.S); the American Heart Association (S.A.S.); Foundation Fighting Blindness (K.P.); and Research to Prevent Blindness.
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 2369. doi:https://doi.org/
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    • Get Citation

      Philip Kiser, Alexander V Kolesnikov, Jianying Kiser, Zhiqian Dong, Bhagirath Chaurasia, Liping Wang, Scott Summers, Thanh Hoang, Seth Blackshaw, Neal S Peachey, Vladimir Kefalov, Krzysztof Palczewski; Conditional deletion of Des1 in the mouse retina does not impair the visual cycle in cones. Invest. Ophthalmol. Vis. Sci. 2019;60(9):2369. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : 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 thought to depend in part on an intraretinal visual cycle involving Müller glia that supplies 11-cis-retinaldehyde to cone opsins. Candidate enzymes of this pathway have been reported but their physiological contribution to cone photoresponses remains unknown. Here, we evaluate the role of a candidate retinol isomerase of this pathway, sphingolipid δ(4) desaturase 1 (Des1).

Methods : Des1 expression in the mouse retina was evaluated by single cell RNAseq. Cone functional dependence on Müller cell-expressed Des1 was assessed through a conditional knockout approach. Floxed Des1 mice, on a Gnat1-/- background to allow isolated recording of cone-driven photoresponses, were bred to Pdgfrα-Cre mice to delete Des1 in Müller cells. Retinal structure was evaluated by optical coherence tomography. Retinal function was assessed by in vivo and ex vivo electroretinography.

Results : Des1 was expressed not only in Müller glia but also in most other retinal cell types. Conditional knockout of Des1 expression, as demonstrated by tissue-selective Des1 gene recombination and reduced Des1 catalytic activity, caused no gross changes in retinal structure, had no effect on cone sensitivity or dark adaptation, but did slightly accelerate the rate of cone phototransduction termination.

Conclusions : These results indicate that Des1 is not required for cone visual pigment regeneration in the mouse.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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