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EYE IN GRAVES DISEASE--ROLE OF ORBITAL FIBROBLASTS

格雷夫斯病中的眼睛——眼眶成纤维细胞的作用

基本信息

批准号：
6953987
负责人：
REBECCA S BAHN
金额：
$ 27.05万
依托单位：
MAYO CLINIC ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
1991
资助国家：
美国
起止时间：
1991-08-01 至 2005-07-31
项目状态：
已结题

项目摘要

DESCRIPTION: Graves' ophthalmopathy (GO) is an autoimmune eye disorder closed associated with Graves' hyperthyroidsim. There is convincing experimental evidence that the orbital fibroblast (including the preadipocyte fibroblast subpopulation) is the target cell in GO. However, the autoantigen against which the immune response is directed is unknown. The thyrotropin receptor (TSHr) is a prime candidate to be the orbital autoantigen because its involvement would help to explain the close clinical and laboratory associations between GO and hyperthyroidism. In recent studies, the PI has demonstrated the present of TSHr mRNA and protein in orbital adipose/connective tissues from patients with GO, wile TSHr expression was not apparent in normal orbital tissues. In addition, she showed that orbital preadipocyte fibroblasts, cells lacking fucntional TSHr, can be differentiated in vitro into mature TSHr-bearing adipocytes. These and other findings led to hypothesize that: 1)expression of TSHr in the orbit in GO is linked to the induction of adipogenesis in orbital preadipocyte fibroblasts, and that; 2) the adipocyte TSHr is the orbital autoantigen recognized by orbital-infiltrating lymphocytes in GO. The PI plans to examine these hypotheses using our system of cultured orbital preadipocyte fibroblasts derived from pateints with GO. In specific aim I, she will define the fibroblast-like cells present in the orbit in GO and identify factors that modulate adipogenesis in these cells. Experiments in Aim II are designed to characterize the obital TSHr and to clarify the link between TSHr expression and adipogenesis in the orbi. In Aim III, she will determine whether cloned orbital-infiltrating lymphocytes from patients with GO recognize TSHr, or other antigens that are processed "naturally" by autologous antigen-presenting cells. The main goal of the research program is to increase understanding of the orbital immune response in GO in order that novel and more specific therapeutic and preventive strategies for this condition might be developed.

格雷夫斯眼病（GO）是一种自身免疫性眼病

项目成果

期刊论文数量（41）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Immunohistochemical detection and localization of a 72-kilodalton heat shock protein in autoimmune thyroid disease.

自身免疫性甲状腺疾病中 72 千道尔顿热休克蛋白的免疫组织化学检测和定位。

DOI：
10.1210/jcem.74.4.1548334
发表时间：
1992
期刊：
The Journal of clinical endocrinology and metabolism
影响因子：
0
作者：
Heufelder,AE;Goellner,JR;Wenzel,BE;Bahn,RS
通讯作者：
Bahn,RS

Differentiation of human orbital preadipocyte fibroblasts induces expression of functional thyrotropin receptor.

DOI：
10.1210/jcem.84.7.5838
发表时间：
1999-07
期刊：
The Journal of clinical endocrinology and metabolism
影响因子：
0
作者：
R. Valyasevi;Dana Erickson;D. Harteneck;C. Dutton;Armin E. Heufelder;Soma C. Jyonouchi;R. Bahn
通讯作者：
R. Valyasevi;Dana Erickson;D. Harteneck;C. Dutton;Armin E. Heufelder;Soma C. Jyonouchi;R. Bahn

A genomic point mutation in the extracellular domain of the thyrotropin receptor in patients with Graves' ophthalmopathy.

格雷夫斯眼病患者促甲状腺素受体胞外域的基因组点突变。