June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Gene expression in thyroid eye disease relative to other orbital diseases
Author Affiliations & Notes
  • Stephen Planck
    Casey Eye Institute, Oregon Health & Science University, Portland, OR
  • Dongseok Choi
    Public Health and Preventive Medicine, Oregon Health & Science University, Portland, OR
  • Christina Harrington
    Integrated Genomics, Oregon Health & Science University, Portland, OR
  • Craig Czyz
    Department of Ophthalmology, Ohio University, Columbus, OH
  • Roger Dailey
    Casey Eye Institute, Oregon Health & Science University, Portland, OR
  • Peter Dolman
    Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, BC, Canada
  • Gerald Harris
    Department of Ophthalmology, Medical College of Wisconsin, Milwaukee, WI
  • Patrick Stauffer
    Casey Eye Institute, Oregon Health & Science University, Portland, OR
  • David Wilson
    Casey Eye Institute, Oregon Health & Science University, Portland, OR
  • James Rosenbaum
    Casey Eye Institute, Oregon Health & Science University, Portland, OR
    Devers Eye Institute, Legacy Research Institute, Portland, OR
  • Footnotes
    Commercial Relationships Stephen Planck, None; Dongseok Choi, None; Christina Harrington, None; Craig Czyz, None; Roger Dailey, None; Peter Dolman, None; Gerald Harris, None; Patrick Stauffer, None; David Wilson, None; James Rosenbaum, Genentech (C), Abbott (F), Xoma (C), Eyegate (F), Bristol Myers (F), Lux (C), Novartis (C), Regeneron (C), Teva (C), Therakine (F), Mitotech (F), Aquinox (F), Allergan (C), Santen (C)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 2040. doi:
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      Stephen Planck, Dongseok Choi, Christina Harrington, Craig Czyz, Roger Dailey, Peter Dolman, Gerald Harris, Patrick Stauffer, David Wilson, James Rosenbaum; Gene expression in thyroid eye disease relative to other orbital diseases. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2040.

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

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Abstract

Purpose: The pathogenesis of thyroid eye disease (TED) remains incompletely understood. Histological distinction of thyroid eye disease from other orbital diseases is not always possible. We tested the hypothesis that gene expression from orbital tissue from patients with thyroid eye disease would distinguish TED from other causes of orbitopathy.

Methods: We obtained formalin-fixed biopsies from the anterior orbit from 12 patients with TED as well as from 14 patients with nonspecific orbital inflammation (NSOI), 4 patients with sarcoid, 2 patients with granulomatosis with polyangiitis (GPA), and 6 healthy controls. Affymetrix Microarray Chips U133 plus 2.0 that analyze about 47,400 transcripts were used to measure gene expression.

Results: Gene expression from patients with TED could be distinguished from tissue from healthy donors by a two-fold increase in gene expression of 18 genes using a false discovery rate of <0.05. These transcripts included: early growth response 1, cysteine rich angiogenic inducer 61, suppressor of cytokine synthesis 3, phosphodiesterase 4b, and interleukin-6, each of which had been implicated in other studies of TED. In addition, 65 genes showed at least a two-fold decrease in gene expression with an FDR <0.05. Transcripts detected by 291 probe sets were differentially regulated in TED compared to either NSOI or sarcoidosis. In marked contrast to NSOI, sarcoidosis, or GPA, transcripts related to the inflammatory response were far less commonly affected. Principal coordinate analysis indicated that the TED tissues more closely mimicked normal tissue than the tissue from the 3 other entities that were studied.

Conclusions: We believe that this is the first study to compare the expression of genes from patients with TED to gene expression in other orbital diseases. Many of the up regulated transcripts detected by us have also been implicated by other investigators, thus supporting the validity of the approach. Our results indicate that TED is a distinct form of orbital inflammation. Transcripts related to inflammation are relatively under-represented in TED compared to other forms of orbital inflammation.

Keywords: 631 orbit • 557 inflammation • 535 gene microarray  
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