Insights into Meibomian gland function

• Applicant: Professor Dr. Friedrich Paulsen
• Subject Area: Ophthalmology ; Nuclear Medicine, Radiotherapy, Radiobiology
• Term: from 2020 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 439830702

The central objective of the proposal is to gain a basic anatomical understanding of the structure and function of the meibomian glands (MGs) as specialized sebaceous glands. This basic understanding is necessary to gain deeper insights into the pathomechanisms leading to meibomian gland dysfunction, one of the major causes of dry eye disease. Only in this way will it be possible to develop causal therapy approaches for affected patients. In order to understand structural differences and similarities between free sebaceous glands (which include the meibomian glands) and sebaceous glands, a completely newly developed, innovative three-dimensional imaging method called Histo Digital (HiD) will be used to uniquely reconstruct certain aspects in serial sections, such as blood vessels or lymph vessels after antibody marking, as well as the entire anatomical structure. These investigations are performed on human as well as on mouse tissue. To differentiate between a meibocyte cell type and a very similar meibocyte excretory duct cell type, structural and functional aspects between meibocytes and excretory duct epithelial cells of meibomian glands are analyzed using transmission electron microscopy (TEM) and a newly developed slice culture method. The slices and a meibocyte epithelial cell line (HMGEC) will be used for cell culture experiments and subsequently investigated by Sudan staining (lipid imaging) and immunohistochemistry for cytokeratins and cadherin. Furthermore, a first detailed study on a central regulator of sebocyte differentiation - the arylhydrocarbon receptor (AhR) - in meibomian glands will be performed and the effect of an AhR receptor knockdown in cultured meibomian slices and cultured HMGECs will be determined. Finally, a basic understanding of the relevant receptor systems for the regulation of meibomian gland function is investigated. Based on preliminary studies, functional aspects of melanocortin receptors, in particular melanocortin receptor 1 (MC1R) and MC5R, are determined in cell culture experiments and investigated by Sudan staining, real-time PCR, Western blot and ELISAs. A similar experimental approach will be followed for meibocytes to determine functional aspects of cannabinoid receptors and CD26 that have been shown to play a decisive role for sebocytes. The results will lead to a basic understanding of meibocyte structure and function, with which in the second project period central functional pathomechanisms of meibomian gland dysfunction will be recognized as a basis for the development of causal therapy options.

• DFG Programme: Research Grants