原发性闭角型青光眼房水免疫球蛋白的测定及意义

应用单向琼脂免疫扩散法测定原发性闭角型青光眼(PCAG)房水免疫球蛋白水平。53例53眼PCAG房水中均可测出IgG,53眼中仅有7眼房水测出IgA,3眼房水测出IgM,PCAG房水IgG及IgA水平均高于对照组老年性白内障,且有非常显著性差异(P<0.001)。PCAG房水IgG滤过系数为1/67.826,较正常人眼高。结果表明PCAG之血房水屏障功能有破坏,房水免疫反应参与PCAG之发生与发展。     

Effect of Chronically Administered Timolol on Aqueous Humor Flow in Patients with Glaucoma

A prospective analysis of the effect of chronically administered timoloi on the rate of aqueous humor flow through the anterior chamber was performed in 15 eyes of 13 subjects with chronic openangle glaucoma. After one week's treatment, the flow of each treated eye was lower than it had been prior to treatment. After one year's treatment, the flow of 13 of 15 treated eyes was lower than it had been prior to treatment. However, the flow was higher in 12 of 15 eyes after a year's treatment than it had been after a week's treatment. These data suggest that the ciliary body or other structures in the eye must partly adapt to the chronic administration of this drug. The mechanism of the adaptation is unknown.     

原发性急性闭角型青光眼患者房水蛋白质组学分析

目的：探究不同眼压的原发性急性闭角型青光眼（PAACG）患者房水蛋白的差异性表达,寻找青光眼性视神经损伤的可能机制,为青光眼性视神经保护的可能作用靶点提供实验依据。方法：病例对照研究。通过简单随机抽样选取2019年3月至2020年9月期间于吉林大学第二医院眼科中心入院治疗的PAACG患者共88例（88眼）。根据PAACG患者的眼压将88个选定的样本分为2组：A组36个样本,眼压≥50 mmHg（1 mmHg=0.133 kPa）;B组52个样本,眼压≤21 mmHg。以上样本被分为2个队列：发现队列（A组26个样本;B组37个样本）和验证队列（A组10个样本;B组15个样本）。分别通过数据独立采集（DIA）方法和平行反应监测（PRM）方法分析房水蛋白。采用独立样本t检验分析蛋白表达差异。结果：本研究从发现队列的A、B组中63个房水样本中共检测出636个蛋白,去除默认蛋白后得到506个蛋白用于后续分析,其中51个蛋白在发现队列A、B组间差异有统计学意义（P=0.020）在这51个差异蛋白中,A组存在17个蛋白表达上调,B组存在34个蛋白表达上调。抽取上述51个差异蛋白中APOA2、TIMP1、LRP2和VASN进行PRM验证,结果显示这4个差异蛋白在发现队列及验证队列中保持一致。结论：PAACG患者房水中差异蛋白的表达与炎症反应以及小梁网细胞外基质重塑、神经损伤相关,可能是导致青光眼患者眼压升高以及视神经损伤的重要原因。     

Aqueous Humor Dynamics in Historical Perspective

In antiquity the aqueous humor was seen as essential to moisten and nourish the lens— the actual organ of vision—and therefore any loss was believed to lead to blindness. The recuperation of the eye after some aqueous loss during cataract couching and experimental loss in animals slowly undermined this idea in the 16^th and 17^th centuries. In the 18^th century production of aqueous from the ciliary region and its outflow from the anterior chamber, and thus its circulation, was generally accepted. Early in the 19^th century the aqueous was thought to be encapsulated, but by the end of the century the general dynamic principles of aqueous flow as we know them today were experimentally and clinically confirmed. The controversy concerning its mode of production and circulation that took place early in the 20^th century was resolved with the discovery of the aqueous veins and advances in molecular biology.     

原发慢性闭角青光眼房水动力学改变与房角关闭范围,眼压及视功能损害的关系

对40例57眼原发性慢性闭角型青光眼(PCACG)和正常对照组30例60眼,进行了房水荧光素浓度曲线的测定。结果显示,PCACG房角关闭≥:180°组,房水荧光素下降率比对照组减少30.21%,所致视功能损害为青光眼早期和中期改变。而房角关闭≥270°组,房水荧光素下降率比对照组减少58.95%,所致视功能损害主要是青光眼晚期改变。证明PCACG房角关闭范围越大,房水荧光素下降率越低,眼压越高,视功能损害也就越严重。     

青光眼房水免疫球蛋白与C3的测定

报告对青光眼21例30眼手术中抽房水测定免疫球蛋白与补体C_3的含量。结果见原发性青光眼房水IgG平均值13.63mg/100ml,继发性青光眼房水IgG平均值为34mg/100ml,均比正常人房水IgG及老年性白内障房水IgG高。继发性青光眼房水IgA平均值含量为8mg/100ml,比原发性青光眼的IgA平均值为4.38mg/100ml有明显差别,均比国外正常尸眼IgA为高,但比老年性白内障房水IgA为低。继发性青光眼房水补体C_3平均值为12.25mg/100ml,明显高于原发性青光眼的补体C_3平均值4.55mg/100ml,均明显比正常尸眼补体C_3高。     

丝裂霉素C对HAD房水引流物置入术远期疗效的影响

目的:评价丝裂霉素 C(mitomycin C,MMC)对国产 HAD(Hunan aqueous drainage implant,HAD)房水引流物置入术治疗难治性青光眼远期疗效的影响。方法:1995年7月～2001年7月,共为154例(159只眼)难治性青光眼患者施行了HAD房水引流物置入术。所有病例分为两组:MMC组与未用MMC组,其中65只眼术中联合应用MMC(0.4mg/ml,1～5min),94只眼术中未用 MMC。以 6mmHg≤术后眼压≤21mmHg作为手术成功标准,采用Kaplan-Meier寿命表分析术后1～6a.不同时点的手术成功率。结果:术后平均随访54.6mon(12～72mon)。术前平均眼压(46.8±14.5)mmHg;术后1年时眼压为(17.4±10.1)mmHg。术后1～6a手术成功率依次为83.7%,77.2%,72.2%,69.0%,62.5%,57.1%。术后1～5a,MMC组与未用MMC组的手术成功率分别为90.0%、77.3%,87.1%、67.3%,83.3%、61.1%,81.3%、56.7%,75.0%、50.0%;两组间差异有显著性。术后1a时眼部超声图像检查,后部滤过泡的平均高度MMC组为(3.8±0.9)mm,而未用MMC组为(2.1±1.4)mm。术后视力不变或改善的有95只眼(81.9%),两组间无明显差异。术后远期(一年以上)常见的并发症有眼压升高(23例,19.8%)、引流管与周围虹膜粘连(18例,15.5%)、白内障加速形成(15例,12.9%)等,两组间无明显差异,未见MMC的严重并发症发生。结论:HAD房水     

先天性青光眼虹膜血管的超微结构观察

对8例8只先天性青光眼虹膜手术切除标本进行了超微结构观察。结果显示:先天性青光眼的虹膜基质血管明显增多,管腔扩张。部分血管内皮细胞肿胀,基膜层次增多至2～4层。内皮细胞和其基膜分离形成间隙,间隙中可见块状纤维致密物沉积。对上述虹膜基质血管的病理改变及其临床意义进行了讨论。     

Alteration of MCP-1 and MMP-9 in Aqueous Humor Is Associated with Secondary Glaucoma in Fuchs Uveitis Syndrome

ABSTRACT

Purpose

To analyze changes in concentrations of pro- or anti-inflammatory cytokines, chemokines, or metalloproteinases (MMP) in the aqueous humor (AH) in Fuchs uveitis syndrome (FUS) patients with (FUSwG) or without (FUSwoG) secondary glaucoma.     

A Mathematical Model of Aqueous Humor Production and Composition

PurposeWe develop a mathematical model that predicts aqueous humor (AH) production rate by the ciliary processes and aqueous composition in the posterior chamber (PC), with the aim of estimating how the aqueous production rate depends on the controlling parameters and how it can be manipulated.MethodsWe propose a compartmental mathematical model that considers the stromal region, ciliary epithelium, and PC. All domains contain an aqueous solution with different chemical species. We impose the concentration of all species on the stromal side and exploit the various ion channels present on the cell membrane to compute the water flux produced by osmosis, the solute concentrations in the AH and the transepithelial potential difference.ResultsWith a feasible set of parameters, the model predictions of water flux from the stroma to the PC and of the solute concentrations in the AH are in good agreement with measurements. Key parameters which impact the aqueous production rate are identified. A relevant role is predicted to be played by cell membrane permeability to K+ and Cl-, by the level of transport due to the Na⁺-H⁺ exchanger and to the co-transporter of Na⁺/K⁺/2Cl⁻; and by carbonic anhydrase.ConclusionsThe mathematical model predicts the formation and composition of AH, based on the structure of the ciliary epithelium. The model provides insight into the physical processes underlying the functioning of drugs that are adopted to regulate the aqueous production. It also suggests ion channels and cell membrane properties that may be targeted to manipulate the aqueous production rate.     

Long-term Outcomes of Domestic Hunan Aqueous Drainage Implantation in Refractory Glaucoma

 Purpose:To evaluate the long-term outcomes of a non-valved, Chinese-made Hunan aqueous drainage device (HAD) in patients with refractory glaucoma, compared to trabeculectomy. Methods:This was a retrospective observational case series, including 27 patients with refractory glaucoma who either underwent HAD implantation (n=11) or trabeculectomy (n=16). The mean follow-up was 27.9±13.5 (mean±SD) months. Intraocular pressure (IOP), visual acuity and postoperative complications were measured. Results:IOP was significantly lower at the last follow-up in both two groups compared with the baseline IOP (HAD: 58.4 to 10.0 mmHg, P>0.001; trabeculectomy:58.4 to 23.7 mmHg, P<0.001). One week,1 month and 1 year after the operation, the average IOP of the HAD group was significantly lower than that of trabeculectomy group (P<0.05 at all time points). However, , the IOP did not differ significantly between the two groups at the time of last follow-up. Conclusion:HAD implantation serves as a good option to control IOP in refractory glaucoma.     

青光眼的基因治疗:问题与挑战

青光眼基因治疗的靶目标包括眼前节的小梁网和睫状体、眼后节的视网膜神经节细胞等。青光眼基因治疗的策略包括降眼压、视神经保护及抑制滤过术后瘢痕形成等方面。将目的基因导入小梁组织使房水排出阻力增加是一种理想的造模方法。目前虽在青光眼基因治疗领域取得较大进展,但在组织特异性启动子、长时基因表达及副作用等方面尚存在着问题和挑战。     

荧光素浓度曲线法用于青光眼房水动力学

对原发性开角青光眼（POAG）51眼及对照组60眼作了房水荧光素浓度曲线（FCC）的测定，结果显示对照组房水FCC的荧光素下降率为82．61％，而POAG组的下降率为39．585，二者相比，P＜0．001，差别非常显著。POAG组早期（21眼）与中晚期（30眼）的荧光素下降率，分别为65．66％及28．96％，与对照组相比，P＜0．01，差别非常显著，对房水FCC测定作为POAG早期诊断的指标作出建议。     

Changes in Iris Stiffness and Permeability in Primary Angle Closure Glaucoma

PurposeTo evaluate the biomechanical properties of the iris by evaluating iris movement during pupil constriction and to compare such properties between healthy and primary angle-closure glaucoma (PACG) subjects.MethodsA total of 140 subjects were recruited for this study. In a dark room, the anterior segments of one eye per subject were scanned using anterior segment optical coherence tomography imaging during induced pupil constriction with an external white light source of 1700 lux. Using a custom segmentation code, we automatically isolated the iris segments from the AS-OCT images, which were then discretized and transformed into a three-dimensional point cloud. For each iris, a finite element (FE) mesh was constructed from the point cloud, and an inverse FE simulation was performed to match the clinically observed iris constriction in the AS-OCT images. Through this optimization process, we were able to identify the elastic modulus and permeability of each iris.ResultsFor all 140 subjects (95 healthy and 45 PACG of Indian/Chinese ethnicity; age 60.2 ± 8.7 for PACG subjects and 57.7 ± 10.1 for healthy subjects), the simulated deformation pattern of the iris during pupil constriction matched well with OCT images. We found that the iris stiffness was higher in PACG than in healthy controls (24.5 ± 8.4 kPa vs. 17.1 ± 6.6 kPa with 40 kPa of active stress specified in the sphincter region; P < 0.001), whereas iris permeability was lower (0.41 ± 0.2 mm²/kPa s vs. 0.55 ± 0.2 mm²/kPa s; p = 0.142).ConclusionsThis study suggests that the biomechanical properties of the iris in PACG are different from those in healthy controls. An improved understanding of the biomechanical behavior of the iris may have implications for the understanding and management of angle-closure glaucoma.     

青光眼术后5-Fu抗瘢痕形成的实验动物研究(兔眼房水的5-Fu药代动力学研究)

6只新西兰纯种白兔右眼行巩膜咬切术后,第三天球结膜下注射0.5%5～Fu 3mg。采用微量进样器对同一兔眼注射5-Fu前(0点)、注射后0.25、0.5、1、1.5、2、3、4、6、8、12小时不同时点多次采用作房水的5-Fu药代动力学研究。结果:注射后平均40分钟房水中5-Fu浓度吸收达高峰,高峰浓度平均为21.94μg/ml,半衰期平均为28.20分钟,4小时后5-Fu在房水中基本消除。     

The Heredity and Treatment of Angle-closure Glaucoma Secondary to Iris and Ciliary Body Cysts

Three families with peripheral iris and ciliary body cysts are described. The cysts were multiple in 10 of the 11 affected patients, and they were bilateral in 8 of the 11. Angle closure glaucoma secondary to the cysts was present in 4 of the 11 cases. The management of this glaucoma requires a high index of suspicion, careful gonioscopic evaluation and proper medical and/or surgical treatment. Laser therapy for the angle closure caused by pigmented cysts may be curative. Nonpigmented ciliary body cysts are refractory to argon laser treatment and carry a poor prognosis. The cases described suggest an autosomal dominant hereditary pattern. The importance of examination and follow up of healthy relatives of patients with iris and ciliary body cysts is stressed, as early detection and treatment by laser cystotomy may prevent or cure angle closure glaucoma if the disease is diagnosed prior to the establishment of synechial closure.     

Distribution of Pigment Particles in Aqueous Drainage Structures in a DBA/2J Mouse Model of Pigmentary Glaucoma

PurposeTo characterize the distribution of pigment particles in aqueous drainage structures of DBA/2J mice with different intraocular pressure (IOP) levels.MethodsDBA/2J mice were monitored from 9 to 44 weeks of age. IOP measurements were performed periodically. At 12, 20, 28, and 36 weeks, three mice were randomly selected for each time point and divided into three IOP groups. The morphology, size, and quantity of pigment particles in aqueous drainage structures were determined via transmission electron microscopy combined with ImageJ-based analysis. Between-group differences were evaluated with a one-way analysis of variance and Fisher''s least significant difference test.ResultsIn the anterior chamber, 74.2% (187/252) of pigment particles were round (diameter range, 0.20–0.73 µm), and 25.8% (65/252) were oval (length range, 0.35–1.20 µm ). In the high-IOP group (IOP≥15 mmHg), pigment particles in the trabecular meshwork (TM) were more abundant and larger in size than those in the normal-IOP group (P<0.001). All separate pigment particles in the TM of the high-IOP group were >0.4  µm in size. The diameters of round (IOP≤10 mmHg, 0.44±0.13 µm; IOP between 10 and 15 mmHg, 0.57±0.13 µm; IOP≥15 mmHg, 0.61±0.12 µm) and the lengths of oval (0.65±0.14 µm vs. 0.77±0.12 µm vs. 0.88±0.15 µm, respectively) pigment particles in the TM differed among groups (F=27.258 and F=27.295, respectively; both P<0.001). No such differences were discovered in the iris and around Schlemm''s canal (P>0.05).ConclusionsIn DBA/2J mice, large and medium pigment particles (>0.4 µm) seem to play an important role in causing aqueous outflow obstruction and IOP elevation.