Participation of Orbital Fibroblasts in the Inflammation of Graves’ Ophthalmopathy

Abstract

Graves’ ophthlamopathy (GO) is a disease process where the orbital connective tissue and musculature undergo a complex remodeling. Certain aspects of the tissue changes associated with GO are unusual, such as the disordered accumulation of the glycosaminoglycan, hyaluronan (1). Other changes resemble several other diseases inside and distant from the orbit. In early GO, the muscles and fat/connective tissue are inflamed and this inflammation appears to be driven through the infiltration of bone marrow-derived cells including lymphocytes and mast cells (2). It is this population of recruited cells that is currently believed to be the source of pro-inflammatory cytokines that provoke in orbital fibroblasts the expression of several important lipid mediators and cytokines. Later, scar formation is common and probably leads to the irreversible damage seen in advanced disease. We hypothesize that the unusual phenotype of the orbital fibroblast underlies the particular susceptibility of the orbit to the inflammatory reaction and tissue remodeling that are characteristic of GO. Specifically, it would appear that orbital fibroblast activation is a critical step in the pathogenesis of GO and many of the aspects of the disease can be attributed directly to the phenotype of these cells. In this chapter, I will briefly review those aspects of orbital fibroblast biology which appear to set these cells apart from fibroblasts residing in other anatomic regions of the human body and render them particularly adept at mediating inflammation and fibrosis.