April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
CD34+ Fibrocytes May Over-arch the Orbit and Thyroid in Patients with Graves’ Disease and Ophthalmopathy
Author Affiliations & Notes
  • Dolly A. Padovani-Claudio
    Ophthalmology and Visual Sciences, Kellogg Eye Center,
    University of Michigan, Ann Arbor, Michigan
  • Roshini S. Fernando
    Ophthalmology and Visual Sciences, Kellogg Eye Center,
    University of Michigan, Ann Arbor, Michigan
  • Stephen J. Atkins
    Ophthalmology and Visual Sciences, Kellogg Eye Center,
    University of Michigan, Ann Arbor, Michigan
  • Gerard M. Doherty
    General Surgery,
    University of Michigan, Ann Arbor, Michigan
  • Paul G. Gauger
    General Surgery,
    University of Michigan, Ann Arbor, Michigan
  • Barbra S. Miller
    General Surgery,
    University of Michigan, Ann Arbor, Michigan
  • Andrew G. Gianoukakis
    Internal Medicine, Harbor-UCLA Medical Center, Los Angeles, California
  • Raymond S. Douglas
    Ophthalmology and Visual Sciences, Kellogg Eye Center,
    University of Michigan, Ann Arbor, Michigan
  • Terry J. Smith
    Ophthalmology and Visual Sciences, Kellogg Eye Center,
    Internal Medicine,
    University of Michigan, Ann Arbor, Michigan
  • Footnotes
    Commercial Relationships  Dolly A. Padovani-Claudio, None; Roshini S. Fernando, None; Stephen J. Atkins, None; Gerard M. Doherty, None; Paul G. Gauger, None; Barbra S. Miller, None; Andrew G. Gianoukakis, None; Raymond S. Douglas, None; Terry J. Smith, None
  • Footnotes
    Support  National Eye Institute, Research to Prevent Blindness, Midwest Eye Banks
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 5099. doi:https://doi.org/
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      Dolly A. Padovani-Claudio, Roshini S. Fernando, Stephen J. Atkins, Gerard M. Doherty, Paul G. Gauger, Barbra S. Miller, Andrew G. Gianoukakis, Raymond S. Douglas, Terry J. Smith; CD34+ Fibrocytes May Over-arch the Orbit and Thyroid in Patients with Graves’ Disease and Ophthalmopathy. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5099. doi: https://doi.org/.

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

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Abstract

Purpose: : The mechanisms that underlie inflammation and tissue remodeling in Graves’ disease (GD) and thyroid-associated ophthalmopathy (TAO) are not well understood. Moreover, the connection between thyroid and orbit in GD has not yet been identified. Fibrocytes (FC) are bone marrow-derived stem cells involved in tissue remodeling. Phenotypic characteristics of orbital fibroblasts (OF) from TAO patients include expression of CD34, Co1l, TSHR, and IGF-1R suggesting that a subpopulation may be derived from FC. We characterized thyroid fibroblasts (TF) from patients with GD to determine if they might resemble OF.

Methods: : TF from donors with GD were cultured and analyzed by flow cytometry and immunohistochemistry (IHC) for CD34, CD90, Col1, TSHR, IGF-1R, and alpha smooth muscle actin (αSMA). Some cultures were treated with TGF-β (5 ng/mL) for 7 days and assessed for differentiation to myofibroblasts.

Results: : Flow cytometry analysis revealed that a subset of TF from patients with GD co-expressed CD34/Col1/THSR and CD34/Col1/IGF1-R . These findings were confirmed by IHC. TF underwent differentiation into myofibroblasts as was evidenced by upregulated αSMA expression in response to TGF-β.

Conclusions: : A subset of GD-derived TF co-express CD34, Col1, THSR, and IGF1-R suggesting that they 1) resemble OF from patients with TAO and 2) derive from FC. TF from these patients can differentiate into myofibroblasts with upregulated αSMA expression in response to TGF-β. These findings suggest that recruitment of FC to the TAO orbit and GD thyroid may underlie the shared manifestations of GD in the two anatomically distant tissues. Investigation of local factors which target FC trafficking and differentiation may lead to the development of specific therapies.

Keywords: autoimmune disease • flow cytometry • immunohistochemistry 
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