IntroductionDry eye is a condition in which there are insufficient tears to lubricate and nourish the eye. An estimated 25 million Americans are affected by dry eye with an increased prevalence among the elderly. The primary cause of dry eye is a lipid deficiency, responsible for 64% of all cases.

Meibomian Gland DysfunctionThe meibomian glands are responsible for the secretion of meibum, the oily substance that prevents evaporation of the eyes tear film.Meibomian gland dysfunction (MGD) leads to alteration in the tear film and dry eye.

PPARPeroxisome proliferator activated receptor (PPAR)PPAR maintains maturation of meibocytes and is key to lipid synthesis.Correlated to decreased lipid production with aging.

HypothesisAim 1: Loss of PPAR will result in abnormalities in meibomian gland formation and lipid production, resulting in dry eye symptoms. Aim 2: Molecular mechanism regulating PPAR expression and regulation of lipid synthesis is Notch signaling.

Notch Signaling Pathway

Transgenic Mouse ModelsTwo types:Inducible Tissue SpecificRemoval of gene can be controlledConditional KnockoutWorks during the embryonic phase by binding to Pax-6More severe phenotype

Loss of PPAR - Phenotype

Removal of Notch-1 SignImproper formation of gland, absence of notch signaling is necessary for lipid productionRemoval of Notch-1 Signaling:Control: Notch-1 Signaling present, normal gland formation, lipids present (Oil Red O Staining).Mutant: Notch-1 Signaling absent, improper gland formation, lipids absent.

Loss of PPAR Increased Lining Thickness

Loss of PPAR - Increased protein concentration in tears of mice.Eye lid of a control mouseEye lid of a mutant mouse, displaying lymphatic vessel intrusion into the central cornea

Human Meibomian Gland (hMG) cells - Subjected to two different growth mediums: keratinocyte serum-free medium (KSFM) and our differentiation medium (DMEM/FBS/EGF) that contains more growth factors.Picture: hMG cells in KSFM Medium

PPAR Presence in Differentiation MediumLipid Presence in Differentiation Medium

PPAR Presence in KSFM Medium

Lipid Presence in KSFM Medium

ConclusionLoss of PPAR results in malformed meibomian glands with MGD-like attributes.PPAR is essential to the formation and function of the meibomian glands.Notch signaling is an important regulator of PPAR.