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

我们对2例激素性青光眼患者的3只眼小梁切除术后获得的小梁网细胞外基质进行免疫组织化学染色。结果表明，小梁网外侧细胞外基质包括基底膜样物质的积累增多。结果还显示，IV型胶原蛋白、硫酸肝素型蛋白聚糖和纤维连接蛋白在小梁网中增加。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。采用免疫组化方法检测原发性开角型青光眼（POAG）和剥脱型青光眼（PEX）小梁网TGF-β的表达及房水中细胞因子的浓度。与正常对照组相比，POAG和PE组的小梁网中TGF-β大量积累。POAG患者房水细胞因子浓度明显高于白内障患者。我们通过玻璃体内注射抗vegf抗体贝伐单抗检测了新生血管性青光眼小梁网的形态学变化。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次数。我们检测了新生血管性青光眼小梁网中神经肽-1和血管生成素- ii的免疫组织化学表达。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。采用Western blot技术研究了抗青光眼药物尼普拉地尔α-和β-阻滞剂对培养的人小梁细胞中MMPs和TIMPs产生的影响。本研究提示，尼普拉地洛能使培养的人小梁网细胞增加TIMP-2.5的产生。我们研究了角膜中央厚度（CCT）和角膜曲率半径（CCR）是否会影响非接触式眼压计（NCT）和Goldmann眼压计（GAT）测量CCR、CCT和IOP的一致性。结果表明，CCT和CCR会影响NCT和gat测量的IOP读数的不一致性。我们使用爪蟾卵母细胞系统和电生理技术检测了抗青光眼药物对NMDA受体功能的直接影响。结果表明，噻洛尔和倍他洛尔可能具有通过NR1a亚基N616直接抑制NMDA受体功能的作用。我们对三名患有常染色体显性先天性小喙蚴和性腺发育的家庭后裔进行了超过25年的随访。在25年的随访期间，其中两名受试者的双眼出现了晚发性发育性青光眼。因此，提示先天性小眼珠常与迟发性发育性青光眼的发病率相关。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