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

• 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
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09671813/
• 关键词: MYOC; TIGR protein; TIGR gene; extracellular matrix; immunohistochemistry; goniodysgenetic glaucoma; neovascular glaucoma; iris nevus syndrome; vascular endothelial growth factor; ラミニン; IV型コラーゲン; in situハイブリダイゼーション; VEGF; プロテオグリカン; ヒアルロン酸

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)我们用免疫化学方法检测了MYOC/TIGR蛋白在青光眼和正常小梁网中的定位。光镜免疫组化结果显示，所有标本的小梁网均被抗MYOC/TIGR多克隆抗体染色阳性。细胞外基质染色。在电镜免疫组化中，不仅在小梁细胞的细胞质中看到染色，而且在细胞外基质中看到染色。在细胞外基质中，染色与长间距胶原和细颗粒物质相关。结论：MYOC/TIGR蛋白不仅分布于小梁细胞中，而且还分布于细胞外基质中，并与长间距胶原和细颗粒物质结合。2）对剥脱综合征患者眼球小梁组织进行组织学和免疫组化检查。剥脱纤维被揭示含有蛋白多糖以及一些 ...更多信息 其他大分子。3）对遗传性青光眼兔眼角区进行形态学观察。在青光眼的眼睛的角区，一个厚的异常组织与圆形的细胞嵌入细胞外基质位于下方的丛。厚层组织中可见大量基底板层样细胞外基质。在正常眼中，角区由发育良好的小梁片组成。这些发现支持了这样的假设，即由于虹膜角膜角发育不良而残留的厚的小管下组织是这种类型青光眼的主要原因之一。4）我们对患有新生血管性青光眼的人眼以及患有实验性眼前段新生血管的兔眼的小梁网进行了组织学和免疫化学检查。结果提示，生长因子（VEGF）在眼前段的发育中起重要作用，新生小梁间隙的侵犯与青光眼的发生密切相关。5）免疫组化法研究了正常人眼组织中细胞外基质的定位。结果表明层粘连蛋白和VI型胶原弥漫性分布在小梁网中。6）我们检查了虹膜痣综合征患者左眼小梁切除术获得的小梁组织，表明虹膜痣综合征可能发生血-房水屏障破坏。7）我们使用激光多普勒血流仪检查了富马酸溴长春胺和马来酸噻吗洛尔对脉络膜血流的影响。结果提示，静脉给药可能不会增加脉络膜血流量。少

项目成果

田原昭彦,久保田敏昭,坂本泰二,畑 快右・他: "血管新生緑内障の発症メカニズム-血管新生緑内障の発生病理-" 眼科手術. 12(1). 117-120 (1999)

Akihiko Tahara、Toshiaki Kubota、Taiji Sakamoto、Yoshiaki Hata 等人：“新生血管性青光眼的发展机制 - 新生血管性青光眼的病理学 -”眼科手术 12(1)。

猪俣 孟,田原 昭彦: "眼の組織・病理アトラス157:前部線維柱帯と後部線維柱帯"臨床眼科. 53(12). 1848-1849 (1999)

孟猪俣 (Meng Inomata)、田原明彦 (Akihiko Tahara)：“眼组织学和病理学图谱 157：前小梁网和后小梁网”临床眼科 53(12) (1999)。

Tawara A., Kubota T., Sakamoto T., et al.: "Developmental process of neovascular glaucoma based on histopathological findings"Jpn J Ophthal Sur. 12-1. 117-120 (1999)

Tawara A.、Kubota T.、Sakamoto T.等人：“基于组织病理学发现的新生血管性青光眼的发展过程”Jpn J Ophthal Sur。

田原昭彦,中村多賀雄,吉田綾子,久保田敏昭,他: "虹彩母斑症侯群(iris-nevus syndrome)における虹彩血管の異常"日眼会誌103:259-267. 103(3). 259-267 (1999)

Akihiko Tahara、Tagao Nakamura、Ayako Yoshida、Toshiaki Kubota 等：“虹膜痣综合征中的虹膜血管异常”日本眼科杂志 103：259-267（1999）。

Tawara, A., Kobata, H., Fujisawa, K., et al.: "Mechanism of intraocular pressure elevation during hemodialysis"Curr. Eye Res.. 17(4). 339-347 (1998)

Tawara, A.、Kobata, H.、Fujisawa, K. 等：“血液透析期间眼压升高的机制”Curr。