EYE IN GRAVES' DISEASE--ROLE OF ORBITAL FIBROBLASTS

描述：(调查人员摘要)：格雷夫斯的后果 眼病包括疼痛、炎症、毁容、复视和失明。 远见卓识。目前，这种虚弱疾病的治疗方案 充其量也只是治标不治本。更好的管理方法和改进 临床结果不太可能被开发出来，直到有更好的 对发病机制的认识。临床三合会Graves病 包括甲亢、格雷夫斯眼病和胫前皮肤病。 非甲状腺表现的临床症状和体征 格雷夫斯病是糖胺多糖积聚的结果 (GAG)在眼后间隙、眼外肌体内和 在患病个体的胫前皮肤中。这些亲水性的 大分子是由成纤维细胞在局部产生的。的中心前提是 这项拟议的研究是成纤维细胞合成GAG的紊乱， 在免疫事件的介导下，导致GAG积聚 同时具有Graves眼病和胫前皮肤病的特点。 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。这个 调查人员打算确定(1)特定物种的丰度是否 他们定义的23 kDa的眼后成纤维细胞抗原是 受免疫环境的影响；(2)是否存在差异 热休克蛋白在人成纤维细胞中的表达 未受影响的解剖区域；(3)主要部位是否有差异 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解剖区域的成纤维细胞；以及(4)如果Gag 眼后、眼外肌周围和胫前成纤维细胞的合成 受到IL-1、其他细胞因子或条件培养液的刺激。这个 调查人员每年看到600-1000名格雷夫斯眼病患者 梅奥诊所，其中大约30人接受眼眶减压 做手术。因此，他们可以接触到非常大的患者群体 这种情况，以及手术组织受到严重影响 个人。使用的技术包括GAG的体外检测 成纤维细胞蛋白的合成、免疫印迹分析和 活检标本的免疫细胞化学和免疫荧光检测 来自受影响的个体。调查人员相信，这些研究将 加深他们对疾病发病机制的理解，这将转化为 以改进管理策略并最终获得更好的临床结果。

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.