Study on the pathogenesis and mechanism of the development of thyroid-associated ophthalmopathy

我们对Graves病眼病的发病机制进行了研究。1)甲状腺相关性眼病（TAO）易感基因研究表明，细胞因子、免疫调节剂、转录因子在TAO的发病过程中起重要作用。在相关研究中，我们发现IL-18、ICAM-1和NFkB1基因的多态性与眼病的发生有显著的相关性。另一方面，CTLA-4基因和CD40基因多态性与Graves病相关，但与TAO无关。2)眼眶成纤维细胞中TSH受体的表达及烟酰胺对其的调节作用近期的随机对照试验显示烟酰胺对TAO的作用。我们研究了烟酰胺对眼眶成纤维细胞（前脂肪细胞）脂肪形成的影响以及TSH受体对成纤维细胞表达的影响。我们证实了TSH受体在TAO患者眼眶成纤维细胞中的表达。吡格列酮，一种PPARγ激动剂，诱导脂肪生成和TSH受体mRNA的表达。烟酰胺不影响TSH受体mRNA的表达，但抑制成纤维细胞的增殖。

We have studied the pathogenesis and mechanism of the development of ophthalmopathy in Graves' disease.1) Susceptibility genes to thyroid-associated ophthalmmopathy (TAO)There are much evidence that cytokines, immunomodulators, transcription factors play important roles in the development of TAO.In association studies we have shown that the polymorphisms of the IL-18, ICAM-1 and NFkB1 genes were significantly associated with the development of ophthalmopathy. On the other hand, CTLA-4 gene and CD40 gene polymorphisms were associated with Graves' disease, but not with TAO.2) TSH receptor expression on the orbital fibroblasts and its modulation by nicotinamideA recent randomized controlled trail showed the usefulness of nicotinamide on TAO. We investigated the effect of nicotinamide on cultured orbital fibroblasts (preadipocytes) in adipogenesis and expressions of TSH receptor on the fibroblasts.We confirmed the expression of TSH receptor on orbital fibroblasts derived from patients with TAO. Pioglitazone, a PPARγ agonist, induced adiopogenesis and the expression of TSH receptor mRNA. Nicotinamide did not affect the expression of TSH receptor mRNA, but suppressed the proliferation of the fibroblasts.