On the pivotal role of Elovl3/ELOVL3 in meibogenesis and ocular physiology of mice

Igor Butovich, Amber Wilkerson, Nita Bhat, Anne McMahon, Seher Yuksel

Research output: Contribution to journalArticle

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Abstract

The purpose of this study was to examine the role of Elovl3 gene in meibogenesis and the impact of ELOVL3 protein ablation on the physiology of the mouse ocular surface and Meibomian glands (MGs). Elovl3 knockout, ELOVL3-ablated (E3hom) mice and their wild type littermates (E3wt) were studied side by side. E3hom mice had abnormal ocular phenotypes such as delayed eye opening, weeping eyes, crusty eyelids, eyelid edema, highly vascularized cornea and tarsal plates (TPs), slit eye, and increased tearing that resemble symptoms observed in human subjects with various forms of dry eye, MG dysfunction and blepharitis. Lipid profiling of E3hom TPs was conducted using chromatography and mass spectrometry. The analyses revealed that the lipid composition of E3hom TPs was strikingly different from that of their E3wt littermates. The mutation affected major classes of meibomian lipids - cholesteryl esters, wax esters, and cholesteryl esters of (O)-acylated w-hydroxy fatty acids. The studies illuminated the central role of ELOVL3 in producing C21:0-C29:0 fatty acids, including odd-chain and branched ones. Ablation of ELOVL3 leads to selective changes in the lipid composition of meibum, making E3hom mice instrumental in studying the mechanisms of the biosynthesis of meibum and modeling various pathologies of human ocular surface and adnexa.-Butovich, I. A., Wilkerson, A., Bhat, N., McMahon, A., Yuksel, S. On the pivotal role of Elovl3/ELOVL3 in meibogenesis and ocular physiology of mice.

Original languageEnglish (US)
Pages (from-to)10034-10048
Number of pages15
JournalFASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume33
Issue number9
DOIs
StatePublished - Sep 1 2019

Fingerprint

Ocular Physiological Phenomena
Physiology
Lipids
Cholesterol Esters
Ablation
Meibomian Glands
Fatty Acids
Eyelids
Waxes
Biosynthesis
Pathology
Chromatography
Chemical analysis
Blepharitis
Mass spectrometry
Esters
Hydroxy Acids
Genes
Cornea
Edema

Keywords

  • fatty acid elongation
  • meibomian glands
  • meibum
  • tarsal plates

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

On the pivotal role of Elovl3/ELOVL3 in meibogenesis and ocular physiology of mice. / Butovich, Igor; Wilkerson, Amber; Bhat, Nita; McMahon, Anne; Yuksel, Seher.

In: FASEB journal : official publication of the Federation of American Societies for Experimental Biology, Vol. 33, No. 9, 01.09.2019, p. 10034-10048.

Research output: Contribution to journalArticle

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