Molecular Biologic Study on Etiological Mechanisms and Therapy of Glaucoma

青光眼病因机制及治疗的分子生物学研究

基本信息

批准号：
09671813
负责人：
TAWARA Akihiko
金额：
$ 1.98万
依托单位：
University of Occupational and Environmental Health (1999)Wakayama Medical University (1997-1998)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1999
项目状态：
已结题

项目摘要

1) We immunohistochemically examined the localization of MYOC/TIGR protein in the glaucomatous and normal trabecular meshworks. In light microscopic immunohistochemistry, the trabecular meshworks from all the specimens stained positively with anti-MYOC/TIGR polyclonal antibody. Staining was observed in the extracellular matrix. In electron microscopic immunohistochemistry, staining was seen not only in the cytoplasm of the trabecular cells but also in the extracellular matrix. In the extracellular matrix, staining was associated with the long-spacing collagens and fine granular materials. It is concluded that MYOC/TIGR protein is distributed not only in the trabecular cells but also in the extracellular matrix associating with the long-spacing collagens and fine granular materials.2) The trabecular tissues from enucleated human eyes with exfoliation syndrome were examined histologically and immunohistochemically. Exfoliation fibers were revealed to contain proteoglycans as well as some … More other macromolecules. It was also detected that the iris vessels had some abnormal changes in the syndrome.3) We examined morphologically the angular region of eyes with inherited glaucoma in rabbits. In the angular region of glaucomatous eyes, a thick abnormal tissue with round-formed cells embedded in the extracellular matrix was located just beneath the plexus. A large amount of extracellular matrix of basal lamina-like material was observed in the thick tissue. In normal eyes, the angular region consisted of well-developed trabecular sheets. These findings support the hypothesis that remaining of a thick subcanalicular tissue because of maldevelopment of the iridocorneal angle is one of the main causes of this type of glaucoma.4) We examined the trabecular meshwork from human eyes with neovascular glaucoma, as well as from rabbit eyes with experimental neovascularization in the anterior segment of the eye histologically and immunohistochemically. The results suggested growth factor (VEGF) plays an important role in development of anterior segment of the eye, and that invasion of the newly intertrabecular spaces has close relation to glaucoma manifestation.5) We studied the localization of extracellular matrix in the normal immunohistochemically. The results indicate that laminin and type VI collagen are located diffusely in the trabecular meshwork.6) We examined the trabecular tissue obtained by trabeculectomy from the patient's with iris nevus syndrome in the left eye to show that disruption of the blood-aqueous barrier may occur in iris-nevus syndrome.7) We examined the effects of brovincamine fumarate and timolol maleate on choroidal blood flow using laser Doppler flowmetry. The results indicated that intravenous administration of the drugs might not increase the choroidal blood flow. Less

1)我们用免疫组织化学方法检查了青光眼和正常小梁网中MYOC/TIGR蛋白的定位。在光镜免疫组织化学中，所有标本的小梁网均在细胞外基质中观察到用抗MYOC/TIGR多克隆抗体染色呈阳性。在电子显微镜免疫组织化学中，不仅在小梁的细胞质中观察到染色在细胞外基质中，染色与长间距胶原和细颗粒物质相关。由此得出结论，MYOC/TIGR蛋白不仅分布在小梁细胞中，而且也分布在细胞外基质中。 2)对患有剥脱综合征的去核人眼小梁组织进行组织学和免疫组化检查。脱落纤维被发现含有蛋白聚糖以及一些其他大分子，还检测到虹膜血管在该综合征中存在一些异常变化。3）我们对患有遗传性青光眼的兔子的眼睛的角区域进行了形态学检查。青光眼眼的角部，有一层厚厚的异常组织，细胞外基质内嵌有圆形细胞，位于基底丛的正下方，有大量的细胞外基质。在正常眼睛的厚组织中观察到层状物质，角区域由发育良好的小梁片组成，这些发现支持了这样的假设：由于虹膜角膜角发育不良而残留的厚泪管下组织是主要原因之一。 4) 我们检查了患有新生血管性青光眼的人眼以及眼前段实验性新生血管形成的兔眼的小梁网组织学和免疫组织化学结果表明生长因子（VEGF）在眼前节的发育中起着重要作用，新的小梁间隙的侵袭与青光眼的表现密切相关。5）我们研究了细胞外基质的定位。免疫组织化学结果表明层粘连蛋白和VI型胶原广泛分布于小梁网中。6)我们检查了小梁切除术获得的小梁组织。左眼患有虹膜痣综合征的患者，表明虹膜痣综合征可能会发生血水屏障破坏。7) 我们使用激光多普勒血流计检查了富马酸布长春明和马来酸噻吗洛尔对脉络膜血流的影响。静脉注射药物可能不会增加脉络膜血流量。