Many-faceted Studies on Roles of Extracellular Matrix in Development of Glaucoma

细胞外基质在青光眼发生过程中作用的多方面研究

基本信息

批准号：
16591777
负责人：
TAWARA Akihiko
金额：
$ 2.24万
依托单位：
University of Occupational and Environmental Health, Japan
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2006
项目状态：
已结题

项目摘要

We immunohistochemically stained the extracellular matrixes in the trabecular meshwork obtained by trabeculectomy from 3 eyes of2 patients with steroid-induced glaucoma. The results indicated that there were increased accumulations of extracellular matrix including basement membrane-like materials in the outer part of the trabecular meshwork. The results also showed that type IV collagen, heparan sulphate-type proteoglycan and fibronectin increase in the trabecular meshwork. From this study, it was suggested that increase of the extracellular matrix in the trabecular meshwork may one of the causes of intraocular elevation in steroid-induced glaucoma.1. We examined immunohistochemically expression of TGF-βin the trabecular meshwork from eyes with primary open angle glaucoma ( POAG) and exfoliation glaucoma ( PEX) as well as the concentration of the cytokine in the aqueous humor by the ELISA methods. There were heavy accumulations of TGF-β in the trabecular meshwork from both POAG and PE … More X compared with from normal control. The concentration of the cytokine in the aqueous humor from POAG was statistically higher than that from cataract patients.2. We examined morphological changes in the trabecular meshwork from neovascular glaucoma with intravitreous injection of Bevacizumab, which is an anti-VEGF antibody. The results indicated that Bevacizumab could reduce the number of fenestration in the newly formed vessels of neovascular glaucoma.3. We examined immunohistochemically expression of neuropilin-1 and angiopoietin-II in the trabecular meshwork from eyes with neovascular glaucoma. The results indicated that there were depositions of angiopoietin-II in the trabecular meshwork from eyes with neovascular glaucoma4. We studied the effect of anti-glaucoma drug of nipradilol, both α- and β-blocker, on the production of MMPs and TIMPs in cultured human trabecular cells by using the Western blot technique. From this study, it was suggested that nipradilol has the cultured human trabecular meshwork cells increase the production of TIMP-2.5. We examined whether central corneal thickness ( CCT) and corneal curvature radius( CCR) have influences on the concordance of intraocular pressure ( IOP) readings taken with non-contact tonometer ( NCT) and Goldmann applanation tonometer ( GAT) by measuring CCR, CCT, and IOP using NCT and GAT. The results indicated that CCT and CCR could influence the discordance of IOP readings taken with NCT and GAT.6. We examined the direct effects of anti-glaucoma drugs on NMDA receptor function using a Xenopus oocytes system and electrophysiological techniques. The results suggested that timolol and betaxolol may have an additional role that they directly inhibit NMDA receptor function possibly via N616 of the NR1a subunit.7. We followed up three subjects descended from a family with autosomal dominant congenital microcoria and goniodysgenesis for more than 25 years. Two of these subjects developed late onset developmental glaucoma in both eyes during the 25-years follow-up period. It is, therefore, suggested that congenital microcoria are frequently associated with the incidence of late onset developmental glaucoma. Less

我们通过小梁切除术从2例类固醇诱导的青光眼患者的3眼中通过小梁切除术获得的小梁网中的细胞外基质进行免疫组织化学染色。结果表明，在小梁网的外部，细胞外基质的积累增加，包括基底膜样材料。结果还表明，小梁网中的IV胶原蛋白酶蛋白聚糖蛋白聚糖和纤连蛋白的增加。从这项研究中可以提出，小梁网状工作中细胞外基质的增加可能是类固醇诱导的青光眼中眼内升高的原因之一。1。我们检查了TGF-βin的免疫组织化学表达，这些小梁网络从具有原发性敞开角度青光眼（POAG）和去角色青光眼（PEX）的眼睛以及ELISA方法在水性幽默中的细胞因子的浓度。与正常对照组相比，POAG和PE的小梁网中的TGF-β大量积累。 POAG水性幽默中细胞因子的浓度在统计学上高于白内障患者的浓度。2。我们检查了小梁网状的形态学变化，并通过静脉注射贝伐单抗（贝伐单抗）是一种抗VEGF抗体。结果表明，贝伐单抗可以减少新形成的新生血管青光眼血管中的塞雷特数量。3。我们从具有新生血管青光眼的眼睛的小梁网中检查了神经蛋白-1和血管生成素-II的免疫组织化学表达。结果表明，从具有新生血管的青光眼4的眼睛中，小梁网中有血管蛋白-II的沉积。我们研究了使用Western印迹技术研究了nipradilol的抗云可瘤药物（α-和β受体阻滞剂）对MMP和TIMP的产生的影响。从这项研究中，提出了尼普拉二醇具有培养的人小梁网状细胞增加了TIMP-2.5的产生。我们检查了中央中央厚度（CCT）和角膜曲率半径（CCR）是否会影响眼内压（IOP）读数与非接触式传动机（NCT）和Goldmann施用Tonometer（GAT）进行的一致性，并通过使用NCT和GAT测量CCR，CCR和IOP。结果表明，CCT和CCR可能会影响与NCT和GAT的IOP读数的不一致。6。我们使用爪蟾卵母细胞系统和电生理技术检查了抗云可瘤药物对NMDA受体功能的直接影响。结果表明，Timolol和Betaxolol可能具有额外的作用，它们可以通过NR1A亚基的N616直接抑制NMDA受体功能。7。我们跟进了三名来自常染色体显性占先天性微核心和促性菌作用的家族的受试者超过25年。在25年的随访期间，两只眼睛的两只受试者中有两个发育迟发。因此，这表明先天性微区经常与晚期发育青光眼的事件有关。较少的