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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

我们对 2 名类固醇诱发性青光眼患者的 3 只眼睛通过小梁切除术获得的小梁网中的细胞外基质进行了免疫组织化学染色。结果表明，小梁网外部的细胞外基质（包括基底膜样物质）的积累增加。结果还表明，小梁网中的 IV 型胶原蛋白、硫酸乙酰肝素型蛋白聚糖和纤连蛋白有所增加。本研究提示小梁网细胞外基质的增加可能是类固醇性青光眼眼内抬高的原因之一。 1．我们通过 ELISA 方法检测了原发性开角型青光眼 (POAG) 和剥脱性青光眼 (PEX) 眼小梁网中 TGF-β 的表达以及房水中细胞因子的浓度。与正常对照相比，POAG 和 PE … More X 的小梁网中 TGF-β 大量积累。 POAG房水中细胞因子的浓度明显高于白内障患者房水中细胞因子的浓度。 2．我们通过玻璃体内注射贝伐单抗（一种抗 VEGF 抗体）检查了新生血管性青光眼小梁网的形态变化。结果表明贝伐珠单抗可以减少新生血管性青光眼新生血管的开窗数量。 3．我们通过免疫组织化学方法检测了新生血管性青光眼眼小梁网中神经毡蛋白-1 和血管生成素-II 的表达。结果表明，新生血管性青光眼眼的小梁网中有血管生成素-II 沉积。我们利用蛋白质印迹技术研究了抗青光眼药物尼普地洛（α-阻滞剂和β-阻滞剂）对培养的人小梁细胞中MMPs和TIMPs产生的影响。这项研究表明，尼普地洛可以增加培养的人小梁网细胞的 TIMP-2.5 产量。我们通过使用 NCT 和 GAT 测量 CCR、CCT 和 IOP，检查中央角膜厚度 (CCT) 和角膜曲率半径 (CCR) 是否对非接触式眼压计 (NCT) 和 Goldmann 压平眼压计 (GAT) 测量的眼压 (IOP) 读数的一致性有影响。结果表明，CCT和CCR会影响NCT和GAT的眼压读数的不一致。6。我们使用爪蟾卵母细胞系统和电生理技术检查了抗青光眼药物对 NMDA 受体功能的直接影响。结果表明，噻吗洛尔和倍他洛尔可能还有一个额外的作用，即它们可能通过NR1a亚基的N616直接抑制NMDA受体功能。7．我们对来自常染色体显性先天性小瞳孔和房角发育不全家族后裔的三名受试者进行了超过 25 年的随访。其中两名受试者在 25 年的随访期间双眼均出现迟发性发育性青光眼。因此，有人认为先天性小瞳孔经常与晚发性发育性青光眼的发生有关。较少的