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

应用免疫组织化学方法对2例激素性青光眼患者的3只眼小梁切除后的小梁细胞外基质进行染色。结果表明，小梁网外侧细胞外基质包括基底膜样物质积聚增多。小梁网中IV型胶原、硫酸乙酰肝素型蛋白多糖和纤维连接蛋白表达增加。本研究提示，小梁网细胞外基质的增加可能是激素性青光眼眼内升高的原因之一。应用免疫组织化学方法检测原发性开角型青光眼(POAG)和剥脱性青光眼(PEX)小梁网中转化生长因子-β的表达，并用双抗体夹心法检测房水中细胞因子的浓度。转化生长因子-β在POAG和PE…的小梁网中大量积聚。与正常对照组相比有更多的X。结论：1.POAG患者房水中细胞因子浓度显著高于白内障患者。我们观察了新生血管性青光眼患者玻璃体内注射抗血管内皮生长因子抗体贝伐珠单抗后小梁网的形态变化。结果表明，贝伐单抗可减少新生血管性青光眼新生血管的开窗数目。我们用免疫组织化学方法检测了新生血管性青光眼患者小梁网中神经粘连蛋白-1和血管生成素-II的表达。结果表明，新生血管性青光眼的小梁网中有血管生成素-II的沉积。应用免疫印迹技术研究了抗青光眼药物尼普拉地洛对α和β阻断剂对培养的人眼小梁细胞分泌基质金属蛋白酶和基质金属蛋白酶的影响。本研究提示，尼普拉地洛可促进培养的人眼小梁细胞产生TIMP-2.5。我们通过使用非接触眼压计(NCT)和Goldmann压平眼压计(GAT)测量中央角膜厚度(CCT)、角膜曲率半径(Ccr)和眼压(IOP)读数的一致性，来检验CCT和Ccr是否影响眼压(IOP)读数的一致性。结果表明，CCT和CCR会影响NCT和GAT测量的眼压读数的不一致性。我们利用非洲爪哇卵母细胞系统和电生理技术研究了抗青光眼药物对NMDA受体功能的直接影响。结果提示，噻吗洛尔和倍他洛尔可能通过NR1a亚基的N616直接抑制NMDA受体功能。我们跟踪调查了三名受试者，这些受试者来自一个常染色体显性遗传性先天性小冠毛和性腺发育不全家系，历时超过25年。其中两名受试者在25年的随访期内出现双眼迟发性青光眼。因此，我们认为先天性小角膜与迟发性发育性青光眼的发病率有关。较少

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