Lahooti Hooshang, Parmar Kishan R, Wall Jack R
The Department of Medicine, University of Sydney, Nepean Clinical School, Penrith, NSW, Australia.
Clin Ophthalmol. 2010 May 14;4:417-25. doi: 10.2147/opth.s6534.
Thyroid-associated ophthalmopathy (TAO), or thyroid eye disease, is a complex inflammatory disorder of the eye that, as its name implies, is associated with thyroid disease. TAO can be divided into three subtypes: ocular myopathy, congestive myopathy and mixed congestive and myopathic ophthalmopathy. Although the precise pathophysiology of TAO remains unclear it is likely to reflect an autoimmune reaction involving sensitized T-cells and autoantibodies directed against a thyroid and orbital tissue shared antigen. One well studied candidate in this immune reaction is the thyroid-stimulating hormone receptor (TSH-r), expressed in the orbital fibroblast and pre adipocyte. In our studies of TAO, we have investigated the nature and significance of antibodies targeting other eye muscle and orbital connective tissue (OCT) antigens. Our findings suggest that autoimmunity against the eye muscle antigen calsequestrin and the OCT antigen collagen XIII plays a role in the pathogenesis of TAO. We propose that ocular myopathy and chronic eyelid retraction are due to autoimmunity against skeletal muscle calsequestrin in the extraocular and eyelid muscles, respectively. This may be initiated in the thyroid where calsequestrin expression is upregulated, possibly due to a stimulatory effect of TSH-r antibodies. We also propose that congestive ophthalmopathy results from a reaction against the TSH-r or collagen XIII in orbital fibroblast cell membranes. Further insight into the role of eye muscle and OCT antigens in the pathogenesis of TAO may allow for the development of new therapies to treat the eye disorder and reduce patient morbidity.
甲状腺相关性眼病（TAO），又称甲状腺眼病，是一种复杂的眼部炎症性疾病，顾名思义，它与甲状腺疾病相关。TAO可分为三种亚型：眼型肌病、充血性肌病以及充血性与肌病混合型眼病。尽管TAO的确切病理生理学机制尚不清楚，但很可能反映了一种自身免疫反应，涉及致敏T细胞和针对甲状腺及眼眶组织共同抗原的自身抗体。这种免疫反应中一个经过充分研究的候选对象是促甲状腺激素受体（TSH-r），它在眼眶成纤维细胞和前脂肪细胞中表达。在我们对TAO的研究中，我们调查了靶向其他眼肌和眼眶结缔组织（OCT）抗原的抗体的性质和意义。我们的研究结果表明，针对眼肌抗原肌集钙蛋白和OCT抗原胶原蛋白XIII的自身免疫在TAO的发病机制中起作用。我们提出，眼型肌病和慢性眼睑退缩分别是由于眼外肌和眼睑肌中针对骨骼肌肌集钙蛋白的自身免疫所致。这可能始于甲状腺，在那里肌集钙蛋白表达上调，可能是由于TSH-r抗体的刺激作用。我们还提出，充血性眼病是由针对眼眶成纤维细胞膜中的TSH-r或胶原蛋白XIII的反应引起的。进一步深入了解眼肌和OCT抗原在TAO发病机制中的作用，可能有助于开发新的疗法来治疗这种眼部疾病并降低患者的发病率。
