Trial Lecture – time and place
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Adjudication committee
- First opponent: Assistant Professor Elizabeth Berger, Wayne State University School of Medicine, USA
- Second opponent: Senior Consultant Jukka Moilanen, Helsinki University Central Hospital, Finland
- Third member and chair of the evaluation committee: Professor II Trond Buanes, Faculty of Medicine, University of Oslo
Chair of the Defence
Professor II Egil Johnson, Faculty of Medicine, University of Oslo
Principal Supervisor
Professor Tor Paaske Utheim, Faculty of Odontology, University of Oslo
Summary
Ocular surface inflammatory diseases such as dry eye disease and allergic conjunctivitis are common diseases and the prevalence of these diseases are increasing. Treatment options are limited, and new management methods are warranted.
Omega-3 fatty acid biosynthetic products named resolvins may actively stop inflammation. Resolvins have shown promising results as treatment of inflammatory diseases in the eye, including dry eye disease and allergic conjunctivitis. Before resolvins are used in treatment of ocular inflammatory disorders, the mechanism of action of the resolvins in healthy, non-diseased patients should be understood.
The aim of this project was to determine how the resolvins Resolvin D1 and Resolvin E1 work in healthy conjunctival goblet cells. Conjunctival goblet cells were studied since disruption in secretion of the goblet cell mucin MUC5AC is associated with both dry eye disease and allergic conjunctivitis. MUC5AC also plays an important role in ocular surface health as it lubricates the ocular surface and removes pathogens and allergens from the tear film, thus preventing inflammation.
Goblet cell function was studied in cultured rat and human conjunctival goblet cells. We identified the receptors for resolvin E1 in goblet cells using RT-PCR, western blot and immunohistochemistry. The calcium concentration in the cytosol of goblet cells and the amount of mucin secretion were measured after treatment with specific signaling pathway inhibitors added before stimulation with either resolvin D1 or resolvin E1. Our studies showed that the resolvins activate multiple signaling pathways to stimulate goblet cell mucin secretion. We believe that resolvins are important both in maintenance of ocular surface health and prevention of disease. Thus, resolvins may be potential new treatments of ocular inflammatory diseases.
Additional information
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