Unique attributes of orbital fibroblasts and global alterations in IGF-1 receptor signaling could explain thyroid-associated ophthalmopathy.
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.
Smith
Terry J
TJ
Division of Molecular Medicine, Department of Medicine, Harbor-UCLA Medical Center, Torrance, California 90502, USA.
Tsai
Chieh Chih
CC
Shih
Mei-Ju
MJ
Tsui
Shanli
S
Chen
Beiling
B
Han
Rui
R
Naik
Vibha
V
King
Chris S
CS
Press
Chris
C
Kamat
Shweta
S
Goldberg
Robert A
RA
Phipps
Richard P
RP
Douglas
Raymond S
RS
Gianoukakis
Andrew G
AG
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
D002630:Chemotactic Factors; D017526:Receptor, IGF Type 1; D015232:Dinoprostone
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