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Molecular mechanism of intractable ocular diseases

眼部难治性疾病的分子机制

基本信息

批准号：
10671650
负责人：
OHNO Shigeaki
金额：
$ 2.37万
依托单位：
Yokohama City University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

项目摘要

Intractable ocular diseases often recur, and their visual prognosis is usually poor. We have studied molecular immunology, molecular genetics, and molecular epidemiology of intractable endogenous uveitis, allergic conjunctival diseases, and adenovirus conjunctivitis.In Behcet's disease, the same genetic association with Japanese patients was found in Greek patients, such as HLA-BィイD1*ィエD15101, and MICA-A6. Glucose intolerance was found in patients with Vogt-Koyanagi-Harada disease. Acute inflammatory cytokines were thought to be the main cause of the glucose intolerance, similar to other autoimmune diseases. Soluble intercellular adhesion molecules were important for the determination of disease activity.In allergic conjunctival diseases, soluble ICAM-1, soluble IL-2, and soluble VCAM-1 in the sera were found to play important roles in the pathogenesis. Among them, soluble VCAM-1 was specifically associated with vernal keratoconjunctivitis, and not with the atopic dermatitis. Histamine release test using small amount of whole blood was also revealed to be a useful test for the determination of responsible antigen. In Atopic dermatitis, the patients with ocular manifestation have significantly higher IgE titer against rice and wheat than the patients without ocular manifestation.In adenovirus conjunctivitis, new genointypes of adenovirus 3 were found. We have successfully applied the PCR-sequence method for the detection of adenovirus serotypes. In the study of adertovirus conjunctivitis during the last 10 years, the dominant serotype of various adenoviruses has been changing every 3-5 years. We have also found certain number of herpes virus conjunctivitis and chalamydial conjunctivitis cases.These results indicate that it is important and rewarding to study the molecular mechanisms of various intractable ocular diseases.

难治性眼部疾病经常复发，其视力预后通常较差。我们研究了顽固性内源性葡萄膜炎、过敏性结膜疾病和腺病毒结膜炎的分子免疫学、分子遗传学和分子流行病学，在白塞病中，在希腊患者中发现了与日本患者相同的遗传关联，如HLA-B等位基因D1* HLA-D15101和MICA-A6。Vogt-Koyanagi-Harada病患者存在糖耐量异常。与其他自身免疫性疾病一样，急性炎症细胞因子被认为是葡萄糖耐受不良的主要原因。可溶性细胞间粘附分子（sICAM-1、sIL-2、sVCAM-1）在变应性结膜疾病的发病机制中起重要作用。其中，可溶性VCAM-1与春季角结膜炎特异性相关，而与特应性皮炎无关。使用少量全血的组胺释放试验也被揭示为用于确定责任抗原的有用试验。在特应性皮炎中，有眼部症状的患者对大米和小麦的IgE滴度明显高于无眼部症状的患者，在腺病毒结膜炎中发现了新的腺病毒3型基因型，我们成功地应用PCR-测序法检测腺病毒血清型。在过去10年中对腺病毒结膜炎的研究中，各种腺病毒的优势血清型每3-5年发生变化。我们还发现了一定数量的疱疹病毒性结膜炎和泪点性结膜炎病例，这些结果表明，研究各种难治性眼病的分子机制是重要的和有益的。