Lipid composition determines thermotropic properties of meibum of animals and humans with Meibomian gland disorders.

Meibum - a lipid-rich secretion produced by holocrine Meibomian glands (MG) - plays a central role in maintaining ocular surface homeostasis. Previously, changes in MG lipidomes induced by inactivation of critical genes of meibogenesis, such as and others, were shown to cause MG-dysfunction- and dry eye-like signs in mice. Here, we describe the impact of the lipid composition of meibum on its physiological properties, specifically thermotropic/melting characteristics, using various wild type and mutant animals, and compare them with meibum of healthy humans and patients with abnormal meibum. Meibum samples were analyzed using liquid chromatography/mass spectrometry (LC/MS) and differential scanning microcalorimetry (DSC). We found that changes in the balance between major lipid classes in meibum -wax esters, cholesteryl esters, triacylglycerols and free cholesterol - cause detrimental changes in its properties, leading to the loss of cohesiveness, abnormal expressibility from MG, a decline in its protective functions, and, ultimately, abnormal phenotypes of the eyes and adnexa. We conclude that tested animal species can be valuable models for studying human diseases. A combination of LC/MS and DSC can be a powerful diagnostic tool and may help to determine the molecular reasons of various pathologies in human subjects and animals.