The Pathophysiology of Thyroid Eye Disease

@article{Shan2014ThePO,
  title={The Pathophysiology of Thyroid Eye Disease},
  author={Shannon J. C. Shan and Raymond S. Douglas},
  journal={Journal of Neuro-Ophthalmology},
  year={2014},
  volume={34},
  pages={177–185}
}
Abstract: The pathophysiology of thyroid eye disease (TED) is complex and incompletely understood. Orbital fibroblasts (OFs) seem to be the key effector cells that are responsible for the characteristic soft tissue enlargement seen in TED. They express potentially pathogenic autoantigens, such as thyrotropin receptor and insulin-like growth factor-1 receptor. An intricate interplay between these autoantigens and the autoantibodies found in Graves disease may lead to the activation of OFs, which… 

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...

References

SHOWING 1-10 OF 136 REFERENCES

Pathogenesis of Graves' ophthalmopathy: the role of autoantibodies.

  • T. KhooR. Bahn
  • Biology, Medicine
    Thyroid : official journal of the American Thyroid Association
  • 2007
Evidence from the laboratory suggests that monoclonal TSHr autoantibodies (TRAbs) are potent stimulators of adipogenesis in GO orbital cells, and it is possible that circulating TRAbs in Graves' patients both stimulate overproduction of thyroid hormones and increase orbital adipose tissue volume.

Unique attributes of orbital fibroblasts and global alterations in IGF-1 receptor signaling could explain thyroid-associated ophthalmopathy.

The laboratory group has focused over the last several years on defining the peculiarities of the human orbital fibroblasts as a strategy for shedding more light on the pathologies occurring in TAO, reasoned that unique properties of these cells might ultimately prove the basis for why the manifestations of Graves' disease occur in an anatomically selective manner.

Orbital fibroblast heterogeneity may determine the clinical presentation of thyroid-associated ophthalmopathy.

It is reported that fibroblasts derived from the connective/adipose tissue depot are distinct from those investing the extraocular muscles, and differences in the potential for differentiation may reside with phenotypic attributes downstream from this receptor/ adipogenic transcription factor.

Clinical review 157: Pathophysiology of Graves' ophthalmopathy: the cycle of disease.

  • R. Bahn
  • Medicine, Biology
    The Journal of clinical endocrinology and metabolism
  • 2003
The progression of Graves’ ophthalmopathy and PTD from initiation to subclinical disease to fully developed ocular and dermal manifestations appears to be a positive feedback cycle composed of mechanical, immunological, and cellular processes.

Increased generation of fibrocytes in thyroid-associated ophthalmopathy.

The findings suggest that fibrocytes may participate in the pathogenesis of TAO because they express relevant autoantigens such as IGF-I receptor and functional TSHR and differentially accumulate in orbital tissue in TAO.

Current perspective on the pathogenesis of Graves' disease and ophthalmopathy.

Recent studies related to the molecular mechanisms of the disease pathogenesis and the development of animal models for GD have led to a better understanding of the pathogenesis of GD and GO and have opened up potential new avenues for developing novel treatments.

Graves’ ophthalmopathy: State of the art and perspectives

Progress in the management of the ophthalmopathy has been very limited, and glucocorticoids, orbital radiotherapy and orbital decompression remain the mainstays in GO treatment, while novel treatments, such as somatostatin analogues, antioxidants, cytokine antagonists are currently under investigation.

Immunoglobulins from patients with Graves' disease induce hyaluronan synthesis in their orbital fibroblasts through the self-antigen, insulin-like growth factor-I receptor.

The observation that hyaluronan production is induced by GD-IgG in fibroblasts suggests that the IGF-I receptor and its activating antibodies may represent a key pathway through which important pathogenic events in thyroid-associated ophthalmopathy are mediated.

Increased expression of TSH receptor by fibrocytes in thyroid-associated ophthalmopathy leads to chemokine production.

Frequency of circulating TSHR(+) fibrocytes is markedly increased in patients with TAO, and they express proinflammatory chemokines in response to TSH.
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