title: Unique attributes of orbital fibroblasts and global alterations in IGF-1 receptor signaling could explain thyroid-associated ophthalmopathy.
abstract: Tissue remodeling associated with thyroid-associated ophthalmopathy (TAO) involves the complex interplay between resident cells (endothelium, vascular smooth muscle, extraocular muscle, and fibroblasts) and those recruited to the orbit, including members of the "professional" immune system. Inflammation early in the disease can later culminate in fibrosis and diminished extraocular muscle motility. TAO remains a poorly understood process, in large part because access to tissues early in the disease is limited and because no robust and complete animal models of Graves' disease have yet been devised. Remaining uncertainty as to the identity of a pathogenic autoantigen(s) that underlies lymphocyte trafficking to the orbit complicates matters. These limitations in our understanding of extrathyroidal Graves' disease have resulted in poorly served patients with severe TAO. Therapies have targeted symptoms rather than the underlying disease processes. Our laboratory group has focused over the last several years on defining the peculiarities of the human orbital fibroblasts as a strategy for shedding more light on the pathologies occurring in TAO. We have reasoned that unique properties of these cells might ultimately prove the basis for why the manifestations of Graves' disease occur in an anatomically selective manner. In this brief review we attempt to survey our findings. We believe that they might provide a "roadmap" for further discovery into the pathogenesis of TAO. Clearly, more questions remain than those thus far answered.
authors.affiliation: Division of Molecular Medicine, Department of Medicine, Harbor-UCLA Medical Center, Torrance, California 90502, USA.
authors.forename: Terry J
authors.initials: TJ
authors.lastname: Smith
authors.forename: Chieh Chih
authors.initials: CC
authors.lastname: Tsai
authors.forename: Mei-Ju
authors.initials: MJ
authors.lastname: Shih
authors.forename: Shanli
authors.initials: S
authors.lastname: Tsui
authors.forename: Beiling
authors.initials: B
authors.lastname: Chen
authors.forename: Rui
authors.initials: R
authors.lastname: Han
authors.forename: Vibha
authors.initials: V
authors.lastname: Naik
authors.forename: Chris S
authors.initials: CS
authors.lastname: King
authors.forename: Chris
authors.initials: C
authors.lastname: Press
authors.forename: Shweta
authors.initials: S
authors.lastname: Kamat
authors.forename: Robert A
authors.initials: RA
authors.lastname: Goldberg
authors.forename: Richard P
authors.initials: RP
authors.lastname: Phipps
authors.forename: Raymond S
authors.initials: RS
authors.lastname: Douglas
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Gianoukakis
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002630:Chemotactic Factors / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism*; D049970:Graves Ophthalmopathy / Q000378:metabolism* / Q000503:physiopathology*; D006801:Humans; D007249:Inflammation; D008214:Lymphocytes / Q000378:metabolism; D008954:Models, Biological; D009132:Muscles / Q000378:metabolism; D009915:Orbit / Q000378:metabolism*; D010641:Phenotype; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D002630:Chemotactic Factors; D017526:Receptor, IGF Type 1; D015232:Dinoprostone
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