1. Deficiency in Acyl‐CoA:Wax Alcohol Acyltransferase 2 causes evaporative dry eye disease by abolishing biosynthesis of wax esters
- Author
-
Thomas Trischman, Marcin Golczak, Josie A. Silvaroli, Sylwia Chelstowska, Ilya Bederman, Made Airanthi K. Widjaja-Adhi, and Rony R. Sayegh
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Lipid composition ,Meibomian gland ,Alcohol ,Biochemistry ,Article ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,Acyl-CoA ,0302 clinical medicine ,Biosynthesis ,Internal medicine ,Genetics ,medicine ,Animals ,Molecular Biology ,Wax ,Viscosity ,Lacrimal Apparatus ,Esters ,Mice, Inbred C57BL ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,chemistry ,Tears ,Acyltransferase ,visual_art ,visual_art.visual_art_medium ,Dry Eye Syndromes ,sense organs ,Acyltransferases ,030217 neurology & neurosurgery ,Biotechnology - Abstract
Lipids secreted by the meibomian glands (MGs) of the eyelids are essential to the protection of the eye’s surface. An altered meibum composition represents the primary cause of evaporative dry eye disease (DED). Despite the critical importance of the meibum, its biosynthetic pathways and the roles of individual lipid components remain understudied. Here, we report that the genetic deletion of Acyl-CoA:wax alcohol acyltransferase 2 (AWAT2) causes the obstruction of MGs and symptoms of evaporative DED in mice. The lipid composition of the meibum isolated from Awat2(−/−) mice revealed the absence of wax esters, which was accompanied by a compensatory overproduction of cholesteryl esters. The resulting increased viscosity of meibum led to the dilation of the meibomian ducts, and the progressive degeneration of the MGs. Overall, we provide evidence for the main physiological role of AWAT2 and establish Awat2(−/−) mice as a model for DED syndrome that can be used in studies on tear film-oriented therapies.
- Published
- 2020