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

• Published in: The journal of clinical endocrinology and metabolism Vol. 87; no. 1; pp. 385 - 392
• Main Authors: SMITH, Terry J, KOUMAS, Laura, GAGNON, Annemarie, BELL, Andrea, SEMPOWSKI, Gregory D, PHIPPS, Richard P, SORISKY, Alexander
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 2002
• Subjects: Adipocytes - metabolism; Adipocytes - pathology; Biological and medical sciences; Cell Differentiation; Cells, Cultured; Connective Tissue - metabolism; Connective Tissue - pathology; Endocrinopathies; Fibroblasts - immunology; Fibroblasts - metabolism; Fibroblasts - pathology; Flow Cytometry; Graves Disease - pathology; Humans; Immunohistochemistry; Malignant tumors; Medical sciences; Non tumoral diseases. Target tissue resistance. Benign neoplasms; Orbit - pathology; Phenotype; Receptors, Cytoplasmic and Nuclear - agonists; Receptors, Cytoplasmic and Nuclear - analysis; Receptors, Cytoplasmic and Nuclear - biosynthesis; Thiazoles - pharmacology; Thiazolidinediones; Thy-1 Antigens - analysis; Thyroid. Thyroid axis (diseases); Transcription Factors - agonists; Transcription Factors - analysis; Transcription Factors - biosynthesis; Human; Adipocyte; Adipose tissue; Variability; Glycoprotein; Eye muscle; Cell surface; Peroxisome proliferator; Heterogeneity; Symptomatology; Connective tissue; Phenotype; Skin; Derm; Differentiation; Cell; Fibroblast
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.87.1.385

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.