A Novel Human Primary Meibomian Gland Cell Platform for Dry Eye Therapeutics

Dry eye diseaseDEDaffects visual function and quality of lifeand it is estimated to be prevalent inof adults agedyears old or older worldwide with females representing two thirds of this populationMeibomian glandMGdysfunction is age related and is the leading cause of DEDMuch of what is known about the agerelated changes in MGs has been derived from clinical studies performed in patients that measure functional and morphological changes in young and adult populations or on histopathological samplesbut the cellular and molecular mechanisms behind these changes are not completely understood due to the paucity of primary human tissues and glandsTo datethere is only one reported immortalized meibomian gland epithelial cellMGECline originating from a male donor used for DED researchindicating the need for additional cell lines to be generatedUtilizing our knowledge and previous experience isolating sebocyteswe successfully isolated and propagated MGECs from one donorThis proposal describes an approach to generate and characterize a bank of primary MGECs as well as immortalized cell lines from young and old male and female donors to provide commercially available resources to study MGECs originating from various demographicsUsing these newly generated linesthis proposal also outlines the establishment and validation of a high throughput screen to analyze compounds for their ability to modulate lipid levels in MGECs in search of compounds for a potential therapeutic treatment of DEDThe overall objective of this program is to provide commercially available primary and immortalized MGECs as well as to initiate the identification and characterization of a novel DED therapeutic that targets lipid production in meibomian glands Dry eye disease affectsof the worldwide populationyears old or older with an estimatedmillion people in the United States affected by this diseaseThere is an urgent need for better and more appropriate cell model systems to study the age related progression of this diseaseThis proposal focuses on the generation of primary and immortalized meibomian gland epithelial cells and their use in identifying novel drugs to treat dry eye disease