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Anne McMahon, Seher Yuksel, Amber Wilkerson, Nita Bhat, Igor A Butovich; Defining the Role of ELOVL6 in Meibogenesis in Mice. Invest. Ophthalmol. Vis. Sci. 2019;60(9):4302.
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© ARVO (1962-2015); The Authors (2016-present)
Meibum, composed of a complex lipid mixture, is secreted from eyelid meibomian glands on to the surface of the eye with each eye blink. Qualitative and/or quantitative changes of meibum lipids have been proposed to have a role in the etiology of dry eye disease due to MG dysfunction. Chemically mouse and human meibum are similar and mouse genetic models with selective gene inactivation allow dissection of the contribution of defined lipid biosynthetic pathways to its elaboration. A defining characteristic of multiple meibum lipids is their very long chain fatty acyl residues, >C18. Here the contribution of ELOVL6 activity for meibum synthesis and the ocular consequences of its loss were studied in Elovl6 knockout mice.
Adult control (WT) and homozygous Elovl6 knockout (KO; Moon et al. 2014) mice were studied. Dissected Tarsal plates from 2-4 month old animals were used for lipid or RNA extraction. Lipids were characterized by liquid chromatography-mass spectrometric analysis using authentic lipid standards. Gene expression was examined by mRNA array analysis. Gross ocular characteristics were recorded and structural characterization of eyelids with their embedded tarsal plates was by microscopy following H&E staining.
Elovl6 KO mice, born at mendelian frequencies, were smaller than WT littermates from birth through 2 weeks post wean. They were slower to transition to solid food but then rapidly gained weight to resemble WT. At 2 months KO MG appeared normal but as animals aged MG, initially centrally in the lower eyelids, appeared progressively shorter with loss from the most distal portions occurring first. In KO > 1 year most of the lower eyelid glands were absent with some loss of upper eyelid glands. Lipid analysis demonstrated a disrupted elongation process that affected, among other lipids, major monounsaturated wax esters with m/z 619, 633, 647, and 661.
ELOVL6 activity contributes to synthesis of the meibum lipidome but the finding that some C18 containing WE still remain in the KO MG suggests that either a) C18 containing lipids, derived from the diet, are taken up from the circulation or b) other members of the ELOVL family of enzymes, which are highly expressed in the MG, can elongate C16 to C18 fatty acyl residues. The decrease in the presence of longer chain lipids may have an adverse effect on the properties of meibum due to expected changes in its melting temperatures.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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