Gene Expression in Nonspecific Orbital Inflammatory Disease

非特异性眼眶炎症性疾病中的基因表达

• 批准号: 8206876
• 负责人: JAMES T ROSENBAUM
• 金额: $ 43.74万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-30 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8206876
• 关键词: Adrenal Cortex Hormones; Biological Assay; Biopsy; Blindness; Clinical; Collection; Decision Making; Diagnosis; Diplopia; Disease; Dose; Fatty acid glycerol esters; Formalin; Gene Expression; Gene Expression Microarray Analysis; Gene Expression Profile; Gene Expression Profiling; Genes; Granulomatous; Hamman-Rich syndrome; Heterogeneity; Histology; Histopathology; Hyperthyroidism; Inflammation; Inflammatory; International; Lacrimal gland structure; Malignant Neoplasms; Methods; Molecular; Morbidity - disease rate; Ocular orbit; Oral; Pain; Paraffin Embedding; Pathogenesis; Pathologist; Patients; Pattern; Pharmaceutical Preparations; Pharmacogenomics; Principal Investigator; Sarcoidosis; Scleroderma; Sclerosis; Statistical Data Interpretation; Surgeon; Techniques; Testing; Therapeutic; Time; Tissues; Vision; Wegener' s Granulomatosis; base; experience; improved; insight; novel; orbit muscle; outcome forecast; prognostic; programs; response; success; thyroid associated ophthalmopathies; tissue culture

DESCRIPTION (provided by applicant): Nonspecific orbital inflammation (NSOI) is an inflammatory disease which causes pain, diplopia, and loss of vision. The pathogenesis of NSOI is largely unknown and virtually unstudied. Microarray analysis of gene expression has enjoyed marked success in providing novel insights into disease pathogenesis. In addition, microarray profiling has been used to identify distinct subsets of disease that in many instances are indistinguishable by histopathology. We propose to utilize microarray gene expression profiling from formalin- fixed, paraffin-embedded (FFPE) orbital biopsies to gain insight into the pathogenesis of NSOI. Gene expression patterns from orbital tissue of patients with NSOI will be compared with gene expression patterns from orbital biopsies from patients with thyroid orbitopathy, sarcoidosis, or Wegener's granulomatosis as well as patterns from normal orbital fat, normal lacrimal gland, or extraocular muscle. We hypothesize that patients with NSOI will have distinct patterns of gene expression that will provide insights into the pathogenesis of the disease. Furthermore, we hypothesize that NSOI is a heterogeneous collection of diseases and that this heterogeneity can be definitively demonstrated by gene expression profiling. Finally we hypothesize that gene expression profiling will help in prognostic and therapeutic decision making for patients with this highly morbid diagnosis. PUBLIC HEALTH RELEVANCE: Inflammation within the eye socket or orbit causes pain, double vision, and loss of vision. Several diseases including sarcoidosis, Wegener's granulomatous, Graves' disease (hyperthyroidism) and so called nonspecific orbital inflammatory disease can cause orbital inflammation. We have organized 14 centers from around the world to contribute previously biopsied tissue to analyze tissue patterns of gene expression from patients with orbital inflammation in order to clarify the cause, predict prognosis, and ultimately improve the therapy.

描述(由申请人提供)： 非特异性眼眶炎症(NSOI)是一种导致疼痛、复视和视力丧失的炎症性疾病。NSOI的发病机制在很大程度上是未知的，几乎没有研究。基因表达的微阵列分析在为疾病发病机制提供新的见解方面取得了显著的成功。此外，微阵列图谱已被用来识别在许多情况下组织病理学无法区分的疾病的不同亚组。我们建议利用来自福尔马林固定的石蜡包埋(FFPE)眼眶活检的微阵列基因表达谱来深入了解NSOI的发病机制。NSOI患者眼眶组织的基因表达模式将与甲状腺眼眶病、结节病或韦格纳肉芽肿患者的眼眶活检组织的基因表达模式以及正常眼眶脂肪、正常泪腺或眼外肌的基因表达模式进行比较。我们假设NSOI患者将有不同的基因表达模式，这将为疾病的发病机制提供见解。此外，我们假设NSOI是一个疾病的异质性集合，这种异质性可以通过基因表达谱得到明确的证明。最后，我们假设基因表达谱将有助于这种高度病态诊断的患者的预后和治疗决策。 公共卫生相关性： 眼窝或眼眶内的炎症会导致疼痛、复视和失明。包括结节病、韦格纳肉芽肿、Graves病(甲亢)和所谓的非特异性眼眶炎症性疾病在内的几种疾病都能引起眼眶炎症。我们组织了来自世界各地的14个中心捐献先前活检的组织，以分析眼眶炎症患者的基因表达的组织模式，以澄清原因，预测预后，并最终改进治疗。