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Regulation der Zelladhäsion in Meibomdrüsen und deren Rolle in der Pathogenese des Trockenen Auges
Regulation der Zelladhäsion in Meibomdrüsen und deren Rolle in der Pathogenese des Trockenen Auges
Meibomian glands are modified, holocrine sebaceous glands within the eyelid important for the maintenance of the integrity and health of the ocular surface. These glands produce an oily secret which stabilizes the tear film. Therefore, a dysfunction of the glands (Meibomian Gland Dysfunction, MGD) is nowadays seen as the leading cause of the so- called Dry eye disease (DED). Former in situ research done by our group showed that the number of desmosomes in Meibomian glands increases over time during cell differentiation. What is more, Pemphigus vulgaris, a chronic blistering autoimmune disease caused by autoantibodies against desmosomal cadherins, is very often associated with DED. With this work we firstly wanted to analyse the physiological conditions for the formation of cell-cell-contacts in Meibomian glands and secondly investigate the role of cell cohesion in the pathogenesis of the Meibomian gland dysfunction. We used a stable human meibocyte cell-line (human meibomian gland cells, HMGECs) and started with identifying the perfect conditions for differentiation. We determined two points in time that were associated with an early and a more mature state of differentiation. We then wanted to analyze the exact composition of cell cohesion molecules in Meibomian glands and quantify the adhesion strength during maturation. Desmosomal cadherins were of major interest in the beginning, because they are known to be essential for strong cell cohesion in various tissues. However, this data shows that cell cohesion is regulated differently in Meibomian glands. What is more, there is evidence that the adherens junction component E-cadherin, and not desmosomes, is crucial for the maintenance of physiological processes in Meibocytes.
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Melega, Francesca Maria
2021
Deutsch
Universitätsbibliothek der Ludwig-Maximilians-Universität München
Melega, Francesca Maria (2021): Regulation der Zelladhäsion in Meibomdrüsen und deren Rolle in der Pathogenese des Trockenen Auges. Dissertation, LMU München: Medizinische Fakultät
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Abstract

Meibomian glands are modified, holocrine sebaceous glands within the eyelid important for the maintenance of the integrity and health of the ocular surface. These glands produce an oily secret which stabilizes the tear film. Therefore, a dysfunction of the glands (Meibomian Gland Dysfunction, MGD) is nowadays seen as the leading cause of the so- called Dry eye disease (DED). Former in situ research done by our group showed that the number of desmosomes in Meibomian glands increases over time during cell differentiation. What is more, Pemphigus vulgaris, a chronic blistering autoimmune disease caused by autoantibodies against desmosomal cadherins, is very often associated with DED. With this work we firstly wanted to analyse the physiological conditions for the formation of cell-cell-contacts in Meibomian glands and secondly investigate the role of cell cohesion in the pathogenesis of the Meibomian gland dysfunction. We used a stable human meibocyte cell-line (human meibomian gland cells, HMGECs) and started with identifying the perfect conditions for differentiation. We determined two points in time that were associated with an early and a more mature state of differentiation. We then wanted to analyze the exact composition of cell cohesion molecules in Meibomian glands and quantify the adhesion strength during maturation. Desmosomal cadherins were of major interest in the beginning, because they are known to be essential for strong cell cohesion in various tissues. However, this data shows that cell cohesion is regulated differently in Meibomian glands. What is more, there is evidence that the adherens junction component E-cadherin, and not desmosomes, is crucial for the maintenance of physiological processes in Meibocytes.