Unique properties of orbital connective tissue underlie its involvement in Graves' disease

Orbital connective tissue manifests Graves' disease through unknown pathogenic mechanisms. Currently there exists little insight into the identity of factors initiating and sustaining the inflammatory response and tissue remodeling associated with ophthalmopathy. We hypothesize that orbital fibroblasts represent cells with unusual phenotypes. They exhibit exaggerated responses to pro-inflammatory cytokines. Among these are inductions of prostaglandin E(2) and hyaluronan synthesis. Activation of fibroblasts occurs through the trafficking of lymphocytes and mast cells to the orbit and the local production of cytokines. In this brief article, we review some of the attributes of orbital fibroblasts and their interactions with immune cells that are currently believed to contribute to their role in the pathogenesis of Graves' disease.