基于房角镜和扫频光学相干断层成像的眼球房角反射成像技术探究

目的：利用改进的房角扫频光学相干断层成像技术（SS-OCT）探索在体高分辨率房水流出通道成像的可行性。方法：实证研究法。利用SS-OCT以及房角镜搭建房角镜光学相干断层成像（OCT）用于拍摄眼球虹膜角膜角横断面图像，同时建立了模型眼模型以及在体动物实验模型，并获取了虹膜角膜角的结构。结果：基于自行搭建的房角光学相干断层成像技术（G-OCT），成功获取了眼球房角中小梁网和Schlemm's管的图像，并应用G-OCT来测量房水流出通道，并观察眼压变化对其的影响。在给眼球加压后，可以观测到Schlemm's管随眼球压力变化而容受性发生改变。结论：本研究成功搭建了基于SS-OCT和房角镜的G-OCT系统，并且获得了眼球房角横断面下小梁网的面积与Schlemm's管的面积以及相应的动态变化。     

小梁网泵调控理论及其对青光眼诊疗的启示

 小梁网房水引流功能异常导致眼压升高,是原发性开角型青光眼发生发展的最主要危险因素。房水具有搏动外流的特征,说明小梁网是弹性组织,其弹性状态与Schlemm管腔开放程度、管类瓣膜结构联动和深层巩膜静脉丛的开放与闭合密切相关,表明小梁网对房水的引流具有泵调控机制。本文对小梁网泵调控机制的理论基础、相关检查的临床应用及对青光眼微创手术的启示进行了系统介绍。希望小梁网泵调控理论为了解原发性开角型青光眼发病机制、选择治疗策略、优化和创新手术设计提供新的视角。（眼科,2022,31： 405-412）     

健康人和青光眼患者小梁网-Schlemm管的形态学特征

房水循环障碍导致的眼压升高是青光眼发生发展的主要危险因素。小梁网-Schlemm管途径引流75%～80%的房水，其结构在不同生理条件下发生持续动态变化从而引起眼压波动。大量研究表明青光眼患者眼压升高与小梁网和Schlemm管形态改变之间关系紧密，但目前缺乏系统性综述。本文就健康人和多种类型青光眼患者中小梁网及Schlemm管的形态学特征进行综述，以期为青光眼发病机制、预防和治疗的进一步探究提供参考。     

猪眼经内路准分子激光小梁部分切除术后的形态学研究

目的 研究中国实验用小型猪眼在经内路准分子激光小梁部分切除术（ELT）后，小梁网在一段时间内的形态学变化。方法 对4只小型猪行ELT，分别于术后1h、3d、1周和1个月取眼球，并分别行光学显微镜和扫描电子显微镜的形态学观察。结果 光学显微镜观察发现，在术后1h、3d和1周时，有从前房到Schlemm’s管的通道形成，在术后1个月时有持续的小梁网组织的消融。术后1h时激光作用部位有少量渗出，直到1个月时未见到明显的纤维增生现象。扫描电子显微镜观察发现，4个阶段的标本均可看到小梁网上的直径为200fl,m或400fl,m的洞样结构缺损。在1周和1个月的标本中，可以看到在洞的边缘有轻微的组织愈合缘。结论 ELT可以形成前房到Schlemm’s管的通道，且激光引起的组织消融的作用在术后1个月内持续存在。     

CYP1B1基因缺失小鼠眼前房角组织结构的观察

目的 研究细胞色素P450 181(CYP1B1)基因对小鼠眼前房角组织结构的影响.方法 实验研究.采用成年CYP1B1基因缺失小鼠模型,以同龄C57BL/6J小鼠为对照.通过塑料包埋切片技术,用光学显微镜和透射电子显微镜观察两组小鼠眼前房角组织的形态和超微结构.结果 C57BL/6J小鼠眼前房角组织发育正常;CYP1B1因缺失小鼠存在不同程度的房水引流系统发育畸形,表现为小梁网发育不良,网眼狭窄,小梁细胞结构变异,有时可见小梁柱间有异常存在的均质膜,Schlemm管狭窄或缺失,虹膜突从虹膜根直达全部小梁网.这些异常改变在CYP1B1基因缺失小鼠眼前房角内呈局灶性分布.结论 CYP1B1基因在房角的发育过程中有重要作用,其缺失可导致小梁网、Schlemm管、虹膜突等房水滤过道的结构异常,可能影响房水引流系统的代谢和功能.     

内路准分子激光小梁切开术后的前房角组织病理学改变

目的：研究内路准分子激光小梁切开术(Exciner Lascr Trabeculotomy ab interno,ELT)术后眼部表现及房角组织病理改变，探讨ELT的降压机理。方法：对5只兔共10只眼进行了ELT、观察其术后反应、分别于术后第一周到第五周取标本进行光镜和电镜检查。结果：10只眼中有9只眼术后反应轻微，术中术后无任何并发症；有1只眼因术中损伤虹膜而反应较大。光镜观察显示准分子激光切削部位小梁网断裂，Schlemm氏管有穿通口直接与前房相通。电镜下见早期标本切片上小梁细胞内质网扩张，线粒体肿胀、空泡变性，胞浆水肿，但核质均匀，核膜、胞膜完整。后期未见异常小梁细脑。所有切片上均未发现成纤维细胞。结论：ELT术后，在Schlemm氏管与前房之间可形成房水排出的直接通道，减轻房水外排的阻力，降低眼内压。     

氧化应激对小梁网的损伤

青光跟是一组以视网膜神经节细胞(RGCs)丢失和视野缺损为特征的神经退行性疾病,其病理机制尚不完全清楚,眼压升高被认为是青光眼发生和发展最主要的危险因素.小梁网及Schlemm管是房水引流系统的主要组成部分,其结构或功能异常可引起房水流出的受阻进而引起眼压升高.越来越多的证据表明,氧化损伤可能在人小梁网细胞凋亡、功能障碍及其他退行性改变过程中发挥作用.氧化损伤是体内氧化和抗氧化失衡,从而引起脂质过氧化反应、蛋白质变性、DNA损伤等一系列组织病理损伤的过程.既往研究发现青光眼患者房水中氧化应激标志物水平升高,且氧化应激可引起小梁网细胞DNA氧化损伤、细胞内线粒体氧化损伤和炎症反应.本文就氧化应激在小梁网功能损伤中发挥的作用及可能的机制进行综述.     

兔眼慢性高眼压模型前房角结构的改变

目的 观察复方卡波姆诱导的兔眼慢性高眼压模型前房角结构的改变特征.方法 实验研究.将32只青紫蓝兔随机平均分为8组,分别对其左眼前房内注射0.3%复方卡波姆0.3 ml,对药物诱发的高眼压模型进行观察;再于术后1、2、3、4、6、8、10及12周分别随机处死一组兔,制作眼球标本,观察兔眼的前房角结构变化.结果 随药物诱导时间的延长,兔眼压缓慢升高,高眼压持续时间约3个月.药物诱导后的前房角特征:早期以炎症反应为主,约3周后炎症反应减轻直至消失,4周后前房角以纤维变性为主,部分前房角粘连阻塞;电镜下观察可见角巩膜及葡萄膜处的小梁网扩张变形,轴心胶原和弹力样纤维增生;小梁内皮细胞与小梁带分离,分离的内皮细胞形似淋巴细胞且具有单核巨噬细胞样功能,吞噬的卡波姆颗粒通过Schlemm管内皮细胞的空泡转运;房水从管腔的内皮细胞大空泡数逐渐减少,出现裂孔现象;后期过多的卡波姆颗粒堆积于内皮细胞内,堵塞房水流出通道;诱导后晚期的模型眼前房角胶原增生,结构破坏.结论 复方卡波姆诱导的兔眼慢性高眼压模型房水流出受阻的主要部位在小梁内皮网部.     

准分子激光非穿透性小梁手术的实验研究

目的探讨准分子激光非穿透性小粱手术（NPT）的降眼压效果及术后滤过通道纤维化反应。方法对20只兔（40只眼）随机行常规NPT或激光NPT。激光NPT组用准分子激光扫描切削巩膜床和巩膜瓣的内面，再切削Schlemm管表面巩膜，直至有大量的房水渗出。分别于术前、术后1、3、5d，1周、2周，1、3、6个月测量眼压并观察眼部其他表现。分别于术后1、3、6个月进行组织病理学检查。结果术前、术后两组间眼压变化的差异无统计学意义（P〉0．05）；术后各时间点两组眼压值均低于术前（P〈0．05）；常规NPT组术中有3眼发生小梁网穿破．术后第1d有4眼发生前房闪辉（＋～＋＋），治疗后3d内消失。激光NPT组术中无并发症。组织病理学检查显示，激光NPT组滤过通道纤维化反应均轻于常规NPT组。结论激光NPr能有效地降低眼压，并能减轻滤过通道的纤维化反应。     

光学相干断层扫描血管成像术（OCTA）及共聚焦激光检眼镜（cSLO）眼底成像对脉络膜破裂伤患者检查的临床价值

目的　探讨光学相干断层扫描血管成像术（optical coherence tomography angiography，OCTA）及共聚焦激光检眼镜（confocal scanning laser ophthalmoscope cSLO）眼底成像对脉络膜破裂伤患者检查的临床价值。方法　收集2017年6月至2018年6月在安徽医科大学第二附属医院门诊就诊的脉络膜破裂伤患者12例12眼的资料。应用cSLO和OCTA对患者进行视网膜脉络膜成像，获取图像后重点分析视网膜无血流层（avascular complex，AC）、脉络膜毛细血管层（choriocapillaris，CC）及脉络膜层，以AC、CC层出现异常血管影像为继发脉络膜新生血管的依据。结果　分析收集的图像可以发现脉络膜破裂伤多呈现与视盘平行的条形病灶（10眼）；部分病例伴有新生血管（7眼），多位于AC层，CC层少见。在OCTA图像中视网膜色素上皮断裂最大直径为（1158.8±364.0）μm，cSLO红光眼底成像处相应位置病变边缘距离为（1184.3±350.2）μm，两者比较差异无统计学意义（t=0.43，P>0.05），OCTA与cSLO眼底成像对视网膜色素上皮损伤的检查结果一致。cSLO红光眼底成像中标识视网膜色素上皮病变面积为（2.83±0.77）mm²，OCTA显示的CC层中标识出脉络膜毛细血管缺损面积为（3.63±1.02）mm²，两者比较差异有统计学意义（t=1.71，P<0.05）。7例患者损伤区内AC层出现异常血管影像，其中6例行玻璃体内注射抗血管内皮生长因子药物治疗，新生血管明显消退，但患者视力提高不明显。结论　OCTA与cSLO眼底成像可以准确地反映外伤致脉络膜破裂伤情况，能够指导治疗，由于是无创检查，在随访过程中存在优势。     

The trabecular meshwork outflow pathways: Structural and functional aspects

The major drainage structures for aqueous humor (AH) are the conventional or trabecular outflow pathways, which are comprised of the trabecular meshwork (made up by the uveal and corneoscleral meshworks), the juxtacanalicular connective tissue (JCT), the endothelial lining of Schlemm's canal (SC), the collecting channels and the aqueous veins. The trabecular meshwork (TM) outflow pathways are critical in providing resistance to AH outflow and in generating intraocular pressure (IOP). Outflow resistance in the TM outflow pathways increases with age and primary open-angle glaucoma. Uveal and corneoscleral meshworks form connective tissue lamellae or beams that are covered by flat TM cells which rest on a basal lamina. TM cells in the JCT are surrounded by fibrillar elements of the extracellular matrix (ECM) to form a loose connective tissue. In contrast to the other parts of the TM, JCT cells and ECM fibrils do not form lamellae, but are arranged more irregularly. SC inner wall endothelial cells form giant vacuoles in response to AH flow, as well as intracellular and paracellular pores. In addition, minipores that are covered with a diaphragm are observed. There is considerable evidence that normal AH outflow resistance resides in the inner wall region of SC, which is formed by the JCT and SC inner wall endothelium. Modulation of TM cell tone by the action of their actomyosin system affects TM outflow resistance. In addition, the architecture of the TM outflow pathways and consequently outflow resistance appear to be modulated by contraction of ciliary muscle and scleral spur cells. The scleral spur contains axons that innervate scleral spur cells or that have the ultrastructural characteristics of mechanosensory nerve endings.     

Funktionelle Morphologie der Abflusswege des Kammerwassers und ihre Veränderungen beim Offenwinkelglaukom

Aqueous humor exits the eye through the trabecular and uveoscleral outflow pathways. Under normal conditions intraocular pressure is maintained in the trabecular outflow pathways in which aqueous humor passes through the trabecular meshwork into Schlemm’s canal. Intraocular pressure is generated through an outflow resistance in the juxtacanalicular region which consists of juxtacanalicular tissue and the inner wall endothelium of Schlemm’s canal. The resistance of this region is under the influence of two contractile systems, the anterior longitudinal portion of the ciliary muscle and the contractile myofibroblast-like cells in the trabecular outflow pathways. Resistance is lowered through contraction of the ciliary muscle or relaxation of the contractile cells in the trabecular outflow pathways. In primary open angle glaucoma, resistance in the juxtacanalicular region is abnormally high. The cause of the increase is related to an increased activity in transforming growth factor beta and connective tissue growth factor signaling. The cells of the trabecular meshwork outflow pathways are stimulated to form a stronger contractile phenotype involving both an increase in the actin cytoskeleton and the surrounding fibrillar extracellular matrix. As a result there is an increase in cellular tone in the trabecular outflow pathways leading to an increase in rigidity and outflow resistance.     

原发性开角型青光眼房水外流通路改变的研究进展

原发性开角型青光眼(POAG)是一种以视神经轴索及相关视网膜神经节细胞丢失为特征的视神经病变.眼压升高是POAG最重要的危险因素.大多数POAG患者眼压升高主要是房水外流阻力异常增高所致.小梁网是产生房水排出阻力的主要部位.目前多数研究者认为POAG患者小梁网功能不良与致炎因子表达、细胞老化、氧化应激损伤及细胞质成分减少等因素有关.小梁网细胞本身及细胞外基质的变化均可以引起房水外流阻力的改变,进而导致眼内压的升高.为了进一步开展对POAG发病机制的研究,有必要就目前有关POAG患者房水外流通路改变的研究进展予以综述,旨在为POAG的深入研究提供参考依据.     

Effects of chemical inhibition of N-WASP, a critical regulator of actin polymerization on aqueous humor outflow through the conventional pathway

The integrity of actin cytoskeletal organization in aqueous humor outflow pathway is thought to play a critical role in modulation of aqueous humor outflow through the trabecular meshwork. Our understanding of the regulation of actin cytoskeletal dynamics in outflow pathway, however, is very limited. To explore the potential importance of Neural Wiskott-Aldrich syndrome protein (N-WASP), a critical regulator of actin polymerization/nucleation in aqueous humor outflow pathway, the effects of Wiskostatin, a selective pharmacological inhibitor of N-WASP, on aqueous humor outflow facility were evaluated using enucleated porcine eyes and a constant pressure perfusion system. Further, drug induced effects on actin cytoskeletal organization, cell adhesions, myosin II phosphorylation, matrix metalloproteinase (MMP) activity, and cytoskeletal protein profile in porcine trabecular meshwork (TM) cells were determined by immunofluorescence, zymography, and mass spectrometry. Aqueous humor outflow facility was increased significantly and progressively in the Wiskostatin perfused porcine eyes. The Wiskostatin perfused eyes appear to exhibit increased giant vacuoles in the inner wall of aqueous plexi and deformation of aqueous plexi. The Wiskostatin treated TM cells demonstrated extensive vacuoles in their cytosol, and both actin stress fibers and focal adhesions were decreased in a reversible manner. The drug-treated TM cells also revealed decreased myosin II and actin in the cytoskeletal enriched triton insoluble fraction but did not affect myosin II phosphorylation or MMP-2 activity. These data demonstrate that the chemical inhibition of N-WASP increases aqueous humor outflow facility in association with decreased actomyosin interaction and cell adhesive interactions revealing the importance of N-WASP in homeostasis of aqueous humor outflow.     

The regulation of trabecular meshwork and ciliary muscle contractility

Current models of aqueous humor outflow no longer treat trabecular meshwork (TM) as an inert tissue passively distended by the ciliary muscle (CM). Instead, ample evidence supports the theory that trabecular meshwork possess smooth muscle-like properties and is actively involved in the regulation of aqueous humor outflow and intraocular pressure. In this model, trabecular meshwork and ciliary muscle appear as functional antagonists, with ciliary muscle contraction leading to a distension of trabecular meshwork with subsequent reduction in outflow. and with trabecular meshwork contraction leading to the opposite effect. Smooth-muscle relaxing substances would therefore appear to be ideal candidates for glaucoma therapy with the dual goal of reducing intraocular pressure via the trabecular meshwork and of improving vascular perfusion of the optic nerve head. However, for such substances to effectively lower intraocular pressure, the effect on the ciliary muscle would have to he minimal. For this reason, more information is needed on the signalling processes involved in regulating trabecular meshwork and ciliary muscle contractility. This review attempts to outline current knowledge of signal transduction pathways leading to relaxation and contraction of ciliary muscle and trabecular meshwork. Pathways can be classified as involving or not involving changes of membrane voltage and of requiring or not requiring external calcium: possibly, other pathways exist. These different pathways involve different ion channels and isoforms of PKC and are expressed to a differing degree in ciliary muscle and trabecular meshwork, leading to differential responses when exposed to relaxing or contracting pharmacological agents. Some of these agents. like tyrosine kinase inhibitors and inhibitors of PKC. have been shown to relax trabecular meshwork while leaving ciliary muscle comparatively unaffected. This profile makes these substances appear as ideal drugs for simultaneously improving ocular outflow and retinal circulation, parameters that determine the time course of visual deterioration in glaucoma.     

Effects of intracameral Na2EDTA and EGTA on aqueous outflow routes in the monkey eye

Intracameral perfusion with 4 to 6 mM Na2EDTA or 4 mM EGTA for 40 to 80 min caused a very large increase in gross outflow facility. This effect was partly reversible when followed by perfusion with mock aqueous humor. Eyes perfused with Na2EDTA were studied morphologically. In the trabecular meshwork the cells separated due to a splitting of the cell junctions. A distention of the cribriform meshwork, a wash-out of extracellular material , and a disintegration of the denuded trabecular cores were also noticed. The inner wall of Schlemm's canal protruded in a "balloonlike" manner into the lumen of the canal and showed frank ruptures, especially after prolonged perfusion times. The conventional outflow pathways beyond Schlemm's canal showed no abnormalities. In the uveoscleral outflow routes the anterior and middle part of the ciliary muscle demonstrated very wide intermuscular clefts and many degenerated muscle fibers. The posterior third of the muscle was normal. So were the ciliary epithelium, the choroid, and the retina. The pupillary sphincter also showed degeneration. The corneal endothelial cells separated, starting at the apical junctional complex.     

Evaluation of confocal microscopy in the analysis of the external trabecular membrane during deep nonpenetrating sclerectomy

PURPOSE: Deep non penetrating sclerectomy (DNPS) is a new filtering surgical procedure whose aim is a selective ablation of the external portion of the trabecular meshwork (TM) which is involved in the aqueous outflow resistance, i.e. the inner wall of Schlemm's canal (SC) and the external trabecular layers, especially the cribriform TM. We evaluated, with a confocal microscope, the structural characteristics of this part of the TM in glaucomatous patients. METHODS: Thirty-six external trabecular membranes (ETM) were obtained from 33 consecutive glaucomatous patients (mean age: 56.5+/-14.5 years) and from four post-mortem normal donors (60.5 +/-7.7 years), which underwent DNPS according to the same surgical procedure. Under conjunctival and scleral flaps, the roof of the SC was opened and removed. A deeper dissection led to the removal of the inner wall of the SC and the adjacent ETM, i.e the TEM, which allowed a satisfactory aqueous flow through the remaining internal TM layers. After fixation with acetone or triton X100 and immunostaining with anti-fibronectin or vimentin antibodies, the samples were analyzed with a confocal microscope (Nikon EZ 2000). RESULTS: The mean thickness of the ETM was 34.4+/-7.3 microm in glaucomatous eyes, not significantly different from the controls (39.0+/-10.7 microm). The main characteristic of the glaucomatous ETM membrane is a paucicellularity as compared to the controls (respectively 21.6+/-12.1 cells/area and 156.1+/-28.8 cells/area). The confocal microscope analysis shows that the ETM involves two different portions of the trabecular meshwork. The architectural characteristics of the outermost portion of the ETM with its star-shaped cells arranged in a homogenous extra-cellular matrix, suggest that it is the trabecular cribriform meshwork. The inner portion of the ETM shows cells arranged regularly in a fibrillar extra-cellular matrix as described in the corneoscleral trabecular meshwork. CONCLUSION: These results confirm the previous reported histopathological changes of the glaucomatous TM. The thickness of the removed ETM and its structural characteristics show that the ablation of the TM layers necessary to obtain a satisfactory aqueous filtration, not only involves the cribriform layers but also one of the inner parts of the TM, i.e. the corneoscleral TM. This result suggests that aqueous humor resistance not only involves the cribriform trabecular meshwork but also a part of the corneoscleral trabecular meshwork.     

Effects of pharmacologic inhibition of protein geranylgeranyltransferase type I on aqueous humor outflow through the trabecular meshwork

PURPOSE: To determine the effects of inhibition of protein geranylgeranyltransferase type I (GGTase-I), which isoprenylates so-called CaaX proteins, including the GTP-binding proteins such as Rho GTPases and the betagamma subunits of heterotrimeric G-proteins, on aqueous humor outflow and trabecular meshwork cytoskeletal integrity. METHODS: A selective small molecular inhibitor of GGTase-I, GGTI-DU40, was tested in this study to investigate its effects on actin cytoskeletal integrity, cell adhesions, cell-cell junctions, myosin II phosphosphorylation, and membrane localization of GTP-binding proteins in trabecular meshwork (TM) cells, using immunofluorescence detection and immunoblotting analysis. The effects of GGTI-DU40 on aqueous humor outflow were determined using organ-cultured, perfused anterior segments of porcine eyes. RESULTS: In the TM cell lysates, GGTI-DU40 was confirmed to inhibit GGTase-I activity in a dose-dependent manner. TM cells treated with GGTI-DU40 displayed dose-dependent changes in cell morphology and reversible decreases in actin stress fibers, focal adhesions, and adherens junctions. Myosin light chain phosphorylation was decreased significantly, and membrane localization of isoprenylated small GTPases and Gbetagamma was impaired in drug-treated TM cells. Aqueous outflow facility was increased significantly in eyes perfused with GGTI-DU40. CONCLUSIONS: These data demonstrate that inhibition of geranylgeranyl isoprenylation of CaaX proteins in the aqueous outflow pathway increases aqueous humor outflow, possibly through altered cell adhesive interactions and actin cytoskeletal organization in cells of the outflow pathway. This study indicates that the GGTase-I enzyme is a promising molecular target for lowering increased ocular pressure in glaucoma patients.     

Confocal microscopic examination of trabecular meshwork removed during ab externo trabeculectomy

AIMS: The aim of the ab externo trabeculectomy (AET) is to remove the external portion of the trabecular meshwork (ETM) responsible for the main aqueous outflow resistance in glaucoma patients, with no opening of the anterior chamber. ETM characteristics were evaluated with a confocal microscope. METHODS: A prospective comparative observational case series was performed in 60 consecutive medically treated patients with primary open angle glaucoma and eight postmortem normal donors' eyes that underwent AET. Once deroofing the Schlemm' s canal (SC), a deeper dissection led to removal of a coherent membrane (ETM) which allowed satisfactory aqueous egress through the remaining intact internal trabecular meshwork (TM) layers. After fixation with acetone and immunostaining with anti-vimentin antibody, ETM were analysed with a confocal microscope. RESULTS: Glaucomatous ETM (mean thickness: 29.5 (7.6) micro m) were characterised by a severe paucicellularity compared with the controls (respectively 37.3 (9.7) cells/area and 167.5 (24.9) cells/area, p<10(-4)). ETM analysis showed involvement of both cribriform and corneoscleral layers. ETM cell density was significantly decreased in case of preoperative fluorometholone instillation. CONCLUSION: Paucicellularity of glaucomatous TM is confirmed by this original technique. Structural characteristics of the ETM, whose removal allows satisfactory aqueous egress, suggest that aqueous outflow resistance not only involves inner wall of SC and juxtacanalicular meshwork but also corneoscleral trabecular layers.     

Functional morphology of the trabecular meshwork in primate eyes

The trabecular meshwork forms most of the resistance to aqueous humor outflow needed for maintenance of a pressure gradient between intraocular pressure of ∼17 mmHg and venous pressure of ∼10 mmHg. The composition of the extracellular material in the subendothelial or cribriform layer seems to be mainly responsible for outflow resistance. The aqueous humor pathways through the subendothelial layer can be influenced by ciliary muscle contraction and presumably also by contractile elements recently found both in trabecular meshwork and scleral spur. Pharmacologically induced disconnection of inner wall and cribriform cells leads to wash out of extracellular material through breaks of the endothelial lining of Schlemm's canal and to increase of outflow facility.In glaucomatous eyes the resistance to aqueous humor outflow is increased due to an increase in different forms of extracellular material deposited within the cribriform layer. The amount of this newly developed extracellular material is correlated with loss of axons in the optic nerve, indicating that a common factor is responsible for both changes.To investigate the effect of various factors on the biology of trabecular cells monolayer cultures derived from cribriform and corneoscleral trabecular meshwork have been established. The two cell lines can be differentiated because cribriform cells in vivo as in vitro stain for αβ-crystallin whereas the corneoscleral cells remain unstained. The effect of TGFβ, a growth factor increased in aqueous humor of glaucomatous eyes and glycocorticoids on trabecular meshwork cells show typical changes in formation of extracellular matrix components and of stress proteins. Dexamethasone and oxidative damage also lead to increase of trabecular meshwork inducible glucocorticoid response (TIGR) protein. A mutation of the TIGR-gene family has recently been found in families with juvenile and chronic simple glaucoma. Future research has to clarify the significance of these genetic factors for the pathophysiology of glaucoma and the role of trabecular cell activity in this respect.