Dry eye disease (DED) affects visual function and quality of life, and it is estimated to be prevalent in 30% of adults aged 50 years old or older worldwide with females representing two-thirds of this population. Meibomian gland (MG) dysfunction is age-related and is the leading cause of DED. Much of what is known about the age- related 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 samples, but the cellular and molecular mechanisms behind these changes are not completely understood due to the paucity of primary human tissues and glands. To date, there is only one reported immortalized meibomian gland epithelial cell (MGEC) line originating from a male donor used for DED research, indicating the need for additional cell lines to be generated. Utilizing our knowledge and previous experience isolating sebocytes, we successfully isolated and propagated MGECs from one donor. This 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 demographics. Using these newly generated lines, this 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 DED. The 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.
Public Health Relevance Statement: Dry eye disease affects 30% of the worldwide population 50 years old or older with an estimated 40 million people in the United States affected by this disease. There is an urgent need for better and more appropriate cell model systems to study the age-related progression of this disease. This 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.
Project Terms: Acetates; Adult; Affect; Age; age related; aged; aging population; Asthenopia; Biological Assay; Biological Models; Blindness; cell age; cell immortalization; Cell Line; Cell model; cell type; Cells; Chronic; Clinical Research; Defect; demographics; Development; Disease; Disease Progression; Epithelial Cells; evaporation; experience; Eye; Eye diseases; eye dryness; Eyelid structure; Female; Film; Future; Generations; Gland; high throughput screening; Human; human tissue; immortalized cell; Inflammation; inhibitor/antagonist; irritation; keratinocyte; Knowledge; Lead; Libraries; Light; Lipids; male; Measures; meibomian gland; meibomian gland dysfunction; Methods; Molecular; Morphology; nile red; novel; novel therapeutics; ocular surface; older patient; Patients; Phase; phase 2 study; Population; Prevalence; prevent; Production; programs; Quality of life; Regimen; Reporting; Research; Resources; Reverse Transcriptase Polymerase Chain Reaction; Sampling; screening; Sebaceous Glands; Sebum; Sjogren's Syndrome; small molecule; SV40 T Antigens; Symptoms; Tarsal plate; Testing; Therapeutic; therapeutic target; Thin Layer Chromatography; Time; Tissues; Treatment Protocols; United States; Validation; Vision; Water; young adult
