June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Sdr16c5 and Sdr16c6 genes control a bifurcation point between meibogenesis and sebogenesis in Meibomian glands of mice by suppressing a dormant biosynthetic pathway
Author Affiliations & Notes
  • Igor A Butovich
    Ophthalmology, The University of Texas Southwestern Medical Center, Dallas, Texas, United States
    The University of Texas Southwestern Medical Center Graduate School of Biomedical Sciences, Dallas, Texas, United States
  • Amber Wilkerson
    Ophthalmology, The University of Texas Southwestern Medical Center, Dallas, Texas, United States
  • Kelly R. Goggans
    Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Natalia Kedishvili
    Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Seher Yuksel
    Ophthalmology, The University of Texas Southwestern Medical Center, Dallas, Texas, United States
  • Footnotes
    Commercial Relationships   Igor Butovich None; Amber Wilkerson None; Kelly Goggans None; Natalia Kedishvili None; Seher Yuksel None
  • Footnotes
    Support  NIH R01 EY027349, AR076924, and DK124921
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 166. doi:
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      Igor A Butovich, Amber Wilkerson, Kelly R. Goggans, Natalia Kedishvili, Seher Yuksel; Sdr16c5 and Sdr16c6 genes control a bifurcation point between meibogenesis and sebogenesis in Meibomian glands of mice by suppressing a dormant biosynthetic pathway. Invest. Ophthalmol. Vis. Sci. 2023;64(8):166.

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

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Abstract

Purpose : Genes SDR16C5/Sdr16c5 and SDR16C6P/Sdr16c6 (a.k.a. Rdhe2/Rdhe2s) encode proteins that belong to a superfamily of short-chain dehydrogenases/reductases (SDRs) in humans and mice. Recently, simultaneous inactivation of Sdr16c5 and Sdr16c6 was shown to be associated with an enlargement of mouse Meibomian and sebaceous glands (MGs and SGs, respectively). SDRs are known to be essential for fatty acid metabolism in various tissues. However, their exact roles in MG physiology and biochemistry are not yet known. The purpose of this study was to establish the role of these enzymes in physiology and biochemistry of MGs and SGs by characterizing, for the first time, the lipid homeostasis in MGs and SGs of Sdr16c5/Sdr16c6 null-mice (DKO) and compare them with wild type (WT) littermates.

Methods : The MG and SG lipids were obtained from WT and DKO mice and analyzed using liquid chromatography/high-resolution mass spectrometry(LC/MS). The structures of lipids were determined using their MS fragmentation, LC retention times, verified using available authentic standards, and quantitated using their total ion abundances. The results were analyzed by means of various multivariate statistical approaches.

Results : Simultaneous inactivation of these genes tripled the overall production of meibum in DKO mice and noticeably altered its lipidomic profile, compared to WT controls, but had a much more subtle effect on sebogenesis. The most prominent changes in the DKO meibum included excessive accumulation of shorter chain sebaceous-type cholesteryl esters (CEs) and wax esters (WEs), and an increase in the degree of unsaturation of Meibomian-type lipids. Importantly, the DKO mice maintained their ability to produce typical extremely long chain Meibomian-type lipids with fatty acid and fatty alcohol chains in the C16 to C34 range. The latter observation indicated preferential activation of the biosynthesis of shorter-chain, sebaceous-type WEs and CEs in the MGs of DKO mice, without altering the elongation patterns of their Meibomian-type counterparts.

Conclusions : It is plausible that Sdr16c5/Sdr16c6 controls a point of bifurcation in one of the meibogenesis subpathways at which biosynthesis of lipids (such as WEs and CEs) in MGs can be redirected toward either abnormal sebaceous-type lipidome in DKO mice, or normal Meibomian-type lipidome in WT mice.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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