Orbital fibroblast heterogeneity may determine the clinical presentation of thyroid-associated ophthalmopathy

J Clin Endocrinol Metab. 2002 Jan;87(1):385-92. doi: 10.1210/jcem.87.1.8164.


Thyroid-associated ophthalmopathy, a process in which the orbital tissues become inflamed and are remodeled, occurs with a variable presentation. In some patients, eye muscle enlargement predominates. In others, the connective/adipose tissue enlargement appears the more significant problem. Orbital fibroblasts exhibit heterogeneous phenotypes in culture. Here we report that fibroblasts derived from the connective/adipose tissue depot are distinct from those investing the extraocular muscles. Connective tissue fibroblasts represent a bimodal population of cells with regard to the surface display of the glycoprotein, Thy-1. Perimysial fibroblasts in contrast express Thy-1 uniformly. In that regard, they resemble those from the skin. When subjected to a newly defined set of culture conditions, adipocyte differentiation occurs in up to 43% of the cells. All adipocytes examined failed to display Thy-1. Fibroblasts derived from perimysium and dermis uniformly do not differentiate into adipocytes when incubated under identical culture conditions. Both Thy-1(+) and Thy-1(-) connective tissue fibroblasts express the adipogenic trigger, peroxisome proliferator activator gamma, suggesting that differences in the potential for differentiation may reside with phenotypic attributes downstream from this receptor/adipogenic transcription factor. These observations enhance our understanding of orbital adipogenesis and define previously unrecognized differences between fibroblasts from the extraocular muscle and connective tissue.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adipocytes / metabolism
  • Adipocytes / pathology
  • Cell Differentiation
  • Cells, Cultured
  • Connective Tissue / metabolism
  • Connective Tissue / pathology
  • Fibroblasts / immunology
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Flow Cytometry
  • Graves Disease / pathology*
  • Humans
  • Immunohistochemistry
  • Orbit / pathology*
  • Phenotype
  • Receptors, Cytoplasmic and Nuclear / agonists
  • Receptors, Cytoplasmic and Nuclear / analysis
  • Receptors, Cytoplasmic and Nuclear / biosynthesis
  • Rosiglitazone
  • Thiazoles / pharmacology
  • Thiazolidinediones*
  • Thy-1 Antigens / analysis
  • Transcription Factors / agonists
  • Transcription Factors / analysis
  • Transcription Factors / biosynthesis


  • Receptors, Cytoplasmic and Nuclear
  • Thiazoles
  • Thiazolidinediones
  • Thy-1 Antigens
  • Transcription Factors
  • Rosiglitazone