PATHOGENESIS OF CONJUNCTIVITIS IN THE EYE

眼结膜炎的发病机制

• 批准号: 2631658
• 负责人: Santa Jeremy Ono
• 金额: $ 25.43万
• 依托单位: SCHEPENS EYE RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-03-01 至 2001-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2631658
• 关键词: alleles; allergens; artificial chromosomes; atopy; clinical research; conjunctivitis; gene expression; genetic markers; genotype; human genetic material tag; human subject; hypersensitivity; immunologic skin test; linkage mapping; major histocompatibility complex; molecular cloning; pathologic process; polymerase chain reaction; questionnaires; seasons; single strand conformation polymorphism; southern blotting; subtraction hybridization

DESCRIPTION: Conjunctivitis is the major atopic disease affecting the ocular surface. Indeed, it is one of the most commonly observed diseases in ophthalmic clinics. Patients with the condition are hypersensitive to normally innocuous substances and suffer from symptoms ranging from mild itching and burning, to chemosis, conjunctival hyperemia, lid edema and at its worst, scarring of the ocular surface and permanent visual impairment. New therapeutic agents are desired due to the side affects of current medications, and the failure of these approaches in severe cases. The design of new drugs require a better understanding of the pathophysiology and biogenesis of the disease. Previous data indicate that while the pathophysiology of atopic conjunctivitis resembles that of rhinitis and asthma, there are also important variables that determine whether allergic inflammation will occur in each, or only a subset of these disparate sites in a particular individual. All data indicate that patients with allergic conjunctivitis share the same atopic condition with rhinitics and asthmatics. The patients with elevated serum gE levels, and the Th2 type cytokines are produced from both Tcells and degranulating mast cells and basophils in the conjunctival epithelium and stroma. However, a large portion of skin test positive individuals would only develop an allergic response in a specific mucosae. The PI hypothesizes that there are particular gene products that specifically target the allergic response to the eye in patients with conjunctivitis, just as they are thought to be specific asthma-predisposing genes. She and others have made significant progress in our efforts to identify potential "atopy" associated markers as well as candidate atopic genes, and will systematically assess the contribution of each of those to atopic conjunctivitis in a large population of patients. Recent progress from her group is included in the preliminary data section of the grant. The first phase of linkage studies will focus on selected markers near (or within) candidate atopic genes. This will be followed by a genomic wide scan for novel determinants using microsatellite markers spaced evenly throughout the human gene map. The PI hopes that the identification of gene products involved in the pathogenesis of allergic conjunctivitis will permit the development of novel therapies for those afflicted with the disease and with other inflammatory diseases of the eye.

描述：结膜炎是影响结膜炎的主要特应性疾病。 眼表 事实上，它是最常见的疾病之一， 眼科诊所 患有这种疾病的患者对 通常无害的物质，并患有从轻度 瘙痒和烧灼感，结膜水肿，结膜充血，眼睑水肿， 最严重的是眼表结疤和永久性视力损害。 由于电流的副作用，需要新的治疗剂。 药物，以及在严重情况下这些方法的失败。 的 新药的设计需要更好地理解病理生理学 和疾病的生物起源。 数据显示，虽然 特应性结膜炎的病理生理学类似于鼻炎， 哮喘，也有重要的变量，决定是否过敏 炎症将发生在这些不同部位的每一个或仅一个子集中 一个特定的个体。 所有数据表明， 结膜炎与鼻炎有相同的特应性病症， 哮喘患者 血清gE水平升高的患者，Th2型 细胞因子由T细胞和脱粒肥大细胞产生， 结膜上皮和基质中的嗜碱性粒细胞。 然而，一个大的 部分皮肤试验阳性的人只会出现过敏反应， 在特定粘膜中的反应。 PI假设有 特定的基因产物，专门针对过敏反应， 结膜炎患者的眼睛，就像他们被认为是 特定的哮喘易感基因 她和其他人已经取得了重大进展， 我们努力确定潜在的“特应性”相关标志物的进展， 以及候选特应性基因，并将系统地评估 在大规模人群中，这些因素对特应性结膜炎的贡献 病人。 她的小组最近的进展包括在初步的 补助金的数据部分。 第一阶段的联系研究将侧重于 候选特应性基因附近（或内部）的选定标记。 这将是 随后使用微卫星进行全基因组扫描以寻找新的决定簇 在人类基因图谱中均匀分布的标记。 PI希望， 过敏性疾病发病机制中基因产物的鉴定 结膜炎将允许开发新的治疗方法， 患有这种疾病和其他眼部炎性疾病。