June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
In-depth genomic and lipidomic comparison of human and rabbit meibomian glands provides clues on the mechanisms of biosynthesis of meibum
Author Affiliations & Notes
  • Igor A Butovich
    Ophthalmology, University of Texas Southwestern Medical Center, Dallas, Texas, United States
  • Jadwiga C Wojtowicz
    Ophthalmology, University of Texas Southwestern Medical Center, Dallas, Texas, United States
  • Anne McMahon
    Ophthalmology, University of Texas Southwestern Medical Center, Dallas, Texas, United States
  • Footnotes
    Commercial Relationships   Igor Butovich, None; Jadwiga Wojtowicz, None; Anne McMahon, None
  • Footnotes
    Support  NIH grants R01EY024324 and R01EY019480 (to IAB); NIH grant P30EY020799; unrestricted grant from The Research to Prevent Blindness
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 4776. doi:
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      Igor A Butovich, Jadwiga C Wojtowicz, Anne McMahon; In-depth genomic and lipidomic comparison of human and rabbit meibomian glands provides clues on the mechanisms of biosynthesis of meibum. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4776.

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

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Abstract

Purpose : Recently, we compared expression patterns of lipid metabolism-related genes in Meibomian glands (MG) of humans and mice, and linked them to their respective lipidomes. The gene expression profiles (GEP) and lipidomes of both species were found to be very similar. However, the complex metabolic pathway that leads to generation of meibum (which we call meibogenesis), apparently, involves hundreds of proteins, whose roles are difficult to elucidate. To advance our knowledge of meibogenesis, we extended our studies into rabbits, who have meibum that is very different from the human one. By analyzing differentially expressed genes in MG of humans and rabbits, and correlating them with their corresponding lipid profiles, we attempted to identify genes and proteins that might be responsible for the biosynthesis of the major lipid components of meibum.

Methods : Specimens of tarsal plates of human subjects (n=4; HTP), mice (2 pooled samples, 6 animals each; MTP) and white rabbits (n=6; RTP) were collected and analyzed using mRNA microarrays, Expression and Transcriptome Analysis Consoles (from Affymetrix), and SigmaStat (Systat Software, Inc.). Samples of human and animal meibum were analyzed by gas and liquid chromatography and ion trap mass spectrometry.

Results : The intraspecies, intersubject variability of GEP in HTP, MTP, and RTP was low (about ±10%, or less, on a log2 scale, Figure 1), with occasional spikes in just a few out of ~300 genes analyzed. The intraspecies, intersubject variability in meibomian lipids (ML) did not exceed ±15% for major ML. However, when GEP in HTP and RTP were compared with each other (Figure 2), the interspecies differences became obvious. The RTP samples showed significantly higher levels of ELOVL1, TECR, FAR1, ACAT1, BCKDHB, ACADL, and LSS, among other genes that encode enzymes, transporters, and effectors, and much lower levels of SCD, ELOVL6, ACSL3, CERS6, ACADSB, and others, compared with HTP. The differences in GEP and ML were linked to a noticeably higher degree of saturation of ML, higher levels of lanosterol (LS) and dehydro-LS, and higher levels of diacylated diols in rabbit meibum, among other differences.

Conclusions : Genomic approaches, used in combination with metabolomic (lipidomic) ones, provided valuable information on the roles of specific enzymes in meibogenesis and other complex metabolic pathways.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

 

 

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