April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Orbital Fibroblasts From Thyroid Eye Disease Patients Differ In Proliferative And Adipogenic Responses Depending On Disease Sub-type
Author Affiliations & Notes
  • Ajay E. Kuriyan
    Flaum Eye Institute,
    University of Rochester Medical Center, Rochester, New York
    Internal Medicine, Mount Sinai Medical Center, Miami, Florida
  • Geniece M. Lehmann
    Environmental Medicine,
    University of Rochester Medical Center, Rochester, New York
  • Charles E. O'Loughlin
    Flaum Eye Institute,
    University of Rochester Medical Center, Rochester, New York
  • Steven E. Feldon
    Flaum Eye Institute,
    University of Rochester Medical Center, Rochester, New York
  • Richard P. Phipps
    Flaum Eye Institute,
    Environmental Medicine,
    University of Rochester Medical Center, Rochester, New York
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 5105. doi:
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      Ajay E. Kuriyan, Geniece M. Lehmann, Charles E. O'Loughlin, Steven E. Feldon, Richard P. Phipps; Orbital Fibroblasts From Thyroid Eye Disease Patients Differ In Proliferative And Adipogenic Responses Depending On Disease Sub-type. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5105.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : Thyroid Eye Disease (TED) is an autoimmune process primarily associated with Graves’ Disease. Imaging is used to classify patients into 2 groups: Type I with expansion of the fat compartment and Type II with enlargement of the extraocular muscles. Some patients have both components. We tested the hypothesis that orbital fibroblasts (OFs) from Type I TED are prone to adipogenesis, whereas OFs from Type II TED are prone to proliferation. We also examined the ability of agents to inhibit OF adipogenesis and proliferation.

Methods: : CT scans and tissue samples were obtained from TED and non-TED patients undergoing orbital surgery at the Flaum Eye Institute. OFs from 3 Type I, 3 Type II, and 2-3 non-TED patients were treated with 5ng/ml transforming growth factor beta (TGFB), 10% fetal bovine serum (FBS), co-culture with autologous T-cells, 10υM pioglitazone, or 10υM 15d-prostaglandin J2 (15d-PGJ2). To assess the effects of treatment agents, OFs were also co-treated with TGFB or 15d-PGJ2 and 10nM dexamethasone, 10υmol/L NS398 (Cox-2 inhibitor), or 20υmol/L indomethacin (Cox-1 and Cox-2 inhibitor). Proliferation and adipogenesis were measured using the tritiated thymidine assay after 72 hr and the AdipoRed assay after 8 d, respectively. A mixed-effects model was used to compare proliferation and adipogenesis of OFs from different patients. One-way ANOVA with Tukey analysis was used to compare the effect of treatments on adipogenesis and proliferation.

Results: : There was a trend toward more proliferation in Type II OFs compared to Type I OFs with autologous T-cell co-culture (P=0.0633). Type II OFs proliferated more with 5ng/ml TGFB (P<0.0001) and 10% FBS (P<0.0001) than Type I OFs. Type I OFs had more adipogenesis than Type II OFs with 5υM 15d-PGJ2 (P=0.0259) and 10υM pioglitazone (P=0.006) treatments. Indomethacin inhibited TGFB-induced proliferation in Type I (P<0.001) and II (P<0.001) OFs and 15d-PGJ2-induced adipogenesis in Type I OFs (P<0.01).

Conclusions: : Type II OFs were driven to proliferate more than Type I OFs, while Type I OFs were driven to adipogenesis more than Type II OFs. This study demonstrates the heterogeneity of OFs from Type I and Type II TED patients. Indomethacin is a potent inhibitor of proliferation and adipogenesis in OFs. Further investigation is required to determine if factors that influence the fate of TED OFs are genetic, environmental, or a combination of the two. Future studies investigating the role of indomethacin in TED are warranted.

Keywords: orbit 
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