EYE IN GRAVES' DISEASE--ROLE OF ORBITAL FIBROBLASTS

  • Bahn, Rebecca Sue (PI)

Project: Research project

Project Details

Description

DESCRIPTION: The consequences of Graves'
ophthalmopathy include pain, inflammation, disfigurement, diplopia and loss
of vision. At present, treatment options for this debilitating condition
are palliative at best. Better approaches to management and improved
clinical outcome will not likely be developed until there is a better
understanding of the pathogenesis. The clinical triad Graves' disease
includes thyrotoxicosis, Graves' ophthalmopathy and pretibial dermopathy.
The clinical signs and symptoms of the nonthyroidal manifestations of
Graves' disease are the result of an accumulation of glycosaminoglycans
(GAG) in the retro-ocular space, within the extra-ocular muscle bodies and
in the pretibial skin of affected individuals. These hydrophilic
macromolecules are produced locally by fibroblasts. The central premise of
the proposed research is that disordered GAG synthesis by fibroblasts,
mediated by immunologic events, results in the GAG accumulation
characteristic of both Graves' ophthalmopathy and pretibial dermopathy.
The investigators will examine fibroblasts from the retro-ocular connective
tissue, extraocular muscles, and pretibial and abdominal skin. The
investigators intend to determine (1) if the abundance of a particular
retro-ocular fibroblast antigen of 23 kDa, which they have defined, is
affected by the immunologic milieu; (2) whether there are differences in
heat shock protein expression between fibroblasts from affected and
unaffected anatomical regions; (3) whether there are differences in major
histocompatibility class II (HLA-DR) or immunoglobulin binding between
fibroblasts from affected and unaffected anatomical regions; and (4) if GAG
synthesis by retro-ocular, extraocular perimysial and pretibial fibroblasts
is stimulated by IL-1, other cytokines or conditioned media. The
investigators see 600-1000 patients with Graves' ophthalmopathy annually at
the Mayo Clinic, approximately 30 of whom undergo orbital decompression
surgery. Thus, they have access to a very large patient population with
this condition, as well as to surgical tissues from severely affected
individuals. Techniques to be used include in vitro assays of GAG
synthesis, immunoblot analyses of fibroblasts proteins, and
immunocytochemical and immunofluorescent examinations of biopsy specimens
from affected individual. The investigators believe these studies will
enhance their understanding of disease pathogenesis which will translate
into improve management strategies and eventually better clinical outcomes.
StatusFinished
Effective start/end date8/1/917/31/05

Funding

  • National Institutes of Health
  • National Institutes of Health: $173,529.00
  • National Institutes of Health
  • National Institutes of Health: $262,067.00
  • National Institutes of Health
  • National Institutes of Health: $270,527.00
  • National Institutes of Health
  • National Institutes of Health: $266,932.00
  • National Institutes of Health: $400,313.00
  • National Institutes of Health
  • National Institutes of Health: $383,925.00
  • National Institutes of Health
  • National Institutes of Health: $393,016.00
  • National Institutes of Health: $393,067.00

ASJC

  • Medicine(all)

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