EYE IN GRAVES' DISEASE--ROLE OF ORBITAL FIBROBLASTS

描述：（研究者摘要）：格雷夫斯的后果 眼病包括疼痛、炎症、毁容、复视和视力下降 视觉。 目前，这种使人衰弱的疾病的治疗方案 最多只能缓解病情 更好的管理方法和改进的 在有更好的治疗方法之前， 了解发病机制。 Graves病临床三联征 包括甲状腺毒症、Graves眼病和胫前皮肤病。 非甲状腺表现的临床体征和症状 格雷夫斯病是糖胺聚糖积累的结果 (GAG)在眼后间隙中，在眼外肌体内， 在受影响个体的胫前皮肤中。 这些亲水性 大分子由成纤维细胞局部产生。 的中心前提 所提出的研究是成纤维细胞的GAG合成紊乱， 由免疫事件介导，导致GAG蓄积 Graves眼病和胫前皮肤病的特征。 研究人员将检查眼后结缔组织中的成纤维细胞， 组织、眼外肌、胫前和腹部皮肤。 的 研究人员打算确定（1）如果一个特定的丰度 他们定义的23 kDa的眼后成纤维细胞抗原， 受免疫环境的影响;（2）是否存在差异， 热休克蛋白在成纤维细胞中的表达 未受影响的解剖区域;（3）是否存在主要差异 组织相容性II类（HLA-DR）或免疫球蛋白结合 来自受影响和未受影响的解剖区域的成纤维细胞;和（4）如果GAG 通过眼后、眼外肌周和胫前成纤维细胞合成 受IL-1、其它细胞因子或条件培养基刺激。 的 研究人员每年观察600-1000名格雷夫斯眼病患者， 马约诊所，其中约30人接受眼眶减压术 手术 因此，他们可以接触到非常大的患者群体， 这种情况，以及手术组织从严重影响 个体 使用的技术包括GAG的体外测定 成纤维细胞蛋白的合成、免疫印迹分析，以及 活检标本的免疫细胞化学和免疫荧光检查 受影响的个人。 研究人员认为，这些研究将 提高他们对疾病发病机制的理解， 改善管理策略并最终改善临床结果。

DESCRIPTION: (Investigator's Abstract): 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.