May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
Thyroid Associated Ophthalmopathy - Cushing’s Disease of the Orbit?
O. M. Durrani; C. U. Onyimba; I. J. Bujalska; J. Abbott; P. Tomlins; T. T. Q. Reuser; G. E. Rose; J. W. Tomlinson; E. A. Walker; S. Rauz
Author Affiliations & Notes
  • O. M. Durrani
    University of Birmingham, Birmingham, United Kingdom
    Academic Unit of Ophthalmology, Division of Immunity and Infection,
  • C. U. Onyimba
    University of Birmingham, Birmingham, United Kingdom
    Academic Unit of Ophthalmology, Division of Immunity and Infection,
    Department of Endocrinology, Division of Medical Sciences,
  • I. J. Bujalska
    University of Birmingham, Birmingham, United Kingdom
    Department of Endocrinology, Division of Medical Sciences,
  • J. Abbott
    University of Birmingham, Birmingham, United Kingdom
    Academic Unit of Ophthalmology, Division of Immunity and Infection,
  • P. Tomlins
    University of Birmingham, Birmingham, United Kingdom
    Academic Unit of Ophthalmology, Division of Immunity and Infection,
  • T. T. Q. Reuser
    University of Birmingham, Birmingham, United Kingdom
    Academic Unit of Ophthalmology, Division of Immunity and Infection,
  • G. E. Rose
    Moorfields Eye Hospital, London, United Kingdom
  • J. W. Tomlinson
    University of Birmingham, Birmingham, United Kingdom
    Department of Endocrinology, Division of Medical Sciences,
  • E. A. Walker
    University of Birmingham, Birmingham, United Kingdom
    Department of Endocrinology, Division of Medical Sciences,
  • S. Rauz
    University of Birmingham, Birmingham, United Kingdom
    Academic Unit of Ophthalmology, Division of Immunity and Infection,
  • Footnotes
    Commercial Relationships O.M. Durrani, None; C.U. Onyimba, None; I.J. Bujalska, None; J. Abbott, None; P. Tomlins, None; T.T.Q. Reuser, None; G.E. Rose, None; J.W. Tomlinson, None; E.A. Walker, None; S. Rauz, None.
  • Footnotes
    Support Wellcome Trust Research, UK; SWBH NHS Trust R&D Major Award 2006
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 3573. doi:
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      O. M. Durrani, C. U. Onyimba, I. J. Bujalska, J. Abbott, P. Tomlins, T. T. Q. Reuser, G. E. Rose, J. W. Tomlinson, E. A. Walker, S. Rauz; Thyroid Associated Ophthalmopathy - Cushing’s Disease of the Orbit?. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3573.

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Abstract

Purpose:: Thyroid-associated ophthalmopathy (TAO) is a sight-threatening autoimmune disease. The clinical features are explained by increased intraorbital volume secondary to inflammatory cell infiltration and tissue-matrix remodelling where adipogenesis has been identified as a fundamental pathogenic mechanism. 11ß-hydroxysteroid dehydrogenase 1 (11ß-HSD1) increases cortisol bioavailability and is pivotal in mediating glucocorticoid (GC) responses in adipose tissue and inflammation. In this study we characterise 11ß-HSD1 as a determinant of the adipogenic pathways in TAO orbital fat (OF) compared to control OF.

Methods:: OF was harvested from 38 clinically inactive TAO and 43 control patients undergoing orbital surgery. GC-mediated adipogenic and inflammatory pathways were examined by a combination of immunohistochemistry, primary preadipocyte cultures, specific enzyme assays, real-time RT-PCR, and colorimetric proliferation assays.

Results:: Histomorphometric analyses of fixed adipose tissue defined smaller TAO adipocytes compared with controls. Primary cultures of TAO OF preadipocytes demonstrated higher 11ß-HSD1 oxo-reductase activity generating cortisol compared to control OF preadipocytes (p<0.05) which was potently regulated by pro-inflammatory cytokines. These results were supported by a greater mRNA expression for 11ß-HSD1 and its regulatory enzyme (hexose-6-phosphate-dehydrogenase) in TAO whole adipose tissue (p<0.05). Expression of glucocorticoid receptor-α mRNA, fatty acid binding protein 4 (marker of adipocyte differentiation) and inflammatory cytokines (IL-1ß, IL-6, TNF-α, TGF-ß2) were significantly higher in TAO OF compared with control OF (p<0.05). Functional studies revealed OF preadipocyte proliferation was regulated by 11ß-HSD1.

Conclusions:: TAO adipocytes are more differentiated and express higher levels of 11ß-HSD1 compared to control OF, whilst local amplification of cortisol increases preadipocyte proliferation. These data suggest that 11ß-HSD1 is a critical determinant of the adipogenic pathways in the TAO OF microenvironment.

Keywords: autoimmune disease • corticosteroids • immunomodulation/immunoregulation 
© 2007, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Permission to republish any abstract or part of an abstract in any form must be obtained in writing from the ARVO Office prior to publication.
Copyright © 2024 Association for Research in Vision and Ophthalmology.
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