Endocrine Abstracts (2017) 49 S12.1 | DOI: 10.1530/endoabs.49.S12.1

The orbital fibroblast: a key player and target for therapy in graves' orbitopathy

Wim Dik

The Netherlands.

Graves’ orbitopathy (GO) is characterized by orbital tissue inflammation, expansion, remodelling and fibrosis. Although the initiating trigger of GO is still indistinct, excessive orbital fibroblast activity is at the heart of its pathogenesis. Orbital fibroblasts are activated by cellular interactions with immune cells and the soluble factors they secrete as well as autoantibodies (e.g. TSH-receptor autoantibodies). Activated orbital fibroblasts produce inflammatory mediators thereby contributing to the inflammatory process in GO. Moreover, orbital fibroblasts exhibit robust proliferative activity and extracellular matrix (especially hyaluronan) synthesizing capacity and can differentiate into adipocytes and myofibroblasts with disease progression, thereby contributing to tissue expansion/remodelling and fibrosis in GO. Orbital fibroblasts, especially those from GO patients, exhibit a hyper-responsive phenotype when compared to fibroblasts from other anatomical regions, which may further contribute to GO pathogenesis. This presentation will address our current view on the role that orbital fibroblasts fulfil in GO pathogenesis as well as the potential of direct targeting of the orbital fibroblast in the treatment of GO.

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