Vascular endothelial growth factor is increased in aqueous humor of glaucomatous eyes

PURPOSE: To assess the concentrations of vascular endothelial growth factor (VEGF) in aqueous humor in eyes with and without glaucoma. METHODS: Concentrations of VEGF were measured using a sandwich ELISA kit in aqueous humor aspirates taken during anterior segment surgery from 87 patients, of whom 54 had glaucoma (27 primary open-angle glaucoma, 8 angle-closure glaucoma, 16 exfoliative glaucoma) and 33 had cataract only. RESULTS: Vascular endothelial growth factor was detected in all samples. The concentration in eyes with cataract only without glaucoma was 102.4 +/- 29.7 pg/mL (mean +/- SD), which was significantly lower than that from eyes with glaucoma (146.7 +/- 51.8 pg/mL). There were no significant differences between primary open-angle glaucoma (140.4 +/- 51.0 pg/mL), angle-closure glaucoma (142.8 +/- 40.2 pg/mL), and exfoliative glaucoma (158.6 +/- 58.9 pg/mL). An unusually high VEGF concentration was detected in one eye with neovascular glaucoma (759 pg/mL) and two eyes with uveitic glaucoma (322 pg/mL). No effect of age, gender, or previous history of medical, laser, or surgical treatment of the aqueous humor VEGF concentration could be detected ( > 0.05). Aqueous humor and plasma VEGF concentrations were measured and compared in 46 patients. The aqueous humor VEGF concentration (144.2 +/- 107.9 pg/mL) was significantly higher ( < 0.01) than the plasma concentration (79.2 +/- 46.1 pg/mL). No significant correlation was found between aqueous humor and plasma VEGF concentrations. CONCLUSION: Aqueous VEGF concentration is increased in eyes with glaucoma.     

Transforming growth factor-β2 levels in aqueous humor of glaucomatous eyes

PURPOSE: To determine whether clinical characteristics are correlated with increased levels of transforming growth factor-beta 2 (TGF-beta 2) in aqueous humor in glaucomatous eyes. METHODS: Aqueous humor samples were collected from 91 glaucomatous eyes. Included were samples from primary open-angle glaucoma (POAG) in 40 eyes, (pseudo)exfoliation syndrome (EXS) in 18 eyes, primary angle-closure glaucoma (PACG) in 26 eyes and uveitis-related secondary glaucoma (SG) in 7 eyes. TGF-beta 2 in aqueous humor was assessed with a specific-capture ELISA. RESULTS: The mean concentration (+/- standard error) of mature (biologically active) TGF-beta 2 in the aqueous humor of eyes with POAG was 293.6 +/- 33.6 pg/ml, significantly higher than that in eyes with PACG, EXS and SG: 147.5 +/- 28.1, 135.8 +/- 30.2 and 41.0 +/- 10.7 pg/ml, respectively (P = 0.0006, P = 0.0010 and P = 0.0003; analysis of variance). The mean concentration (+/- standard error) of total TGF-beta 2 in the aqueous humor of eyes with POAG was 1647.6 +/- 124.5 pg/ml, not significantly different from that in eyes with PACG, EXS and SG: 1482.9 +/- 148.2, 1442.7 +/- 187.8 and 1929.0 +/- 367.6 pg/ml, respectively. A multivariate analysis using logistic regression showed significant correlations between mature TGF-beta 2 concentration and history of cataract surgery (P = 0.0225) and the use of carbonic anhydrase inhibitors (P = 0.0143). CONCLUSIONS: Our results indicate that increased levels of TGF-beta 2 may play an important role in the pathogenesis of POAG.     

Aqueous humor erythropoietin levels in patients with primary open-angle glaucoma

PURPOSE: To evaluate the levels of erythropoietin (EPO) in the aqueous humor in eyes with primary open-angle glaucoma (POAG) and without glaucoma. METHODS: Levels of EPO were measured using a sandwich enzyme-linked immunosorbent assay kit in aqueous humor aspirates taken during anterior segment surgery from 45 patients, of whom 20 had POAG and 25 had senile cataract only. RESULTS: The mean aqueous humor EPO concentration in eyes with POAG (10.91+/-4.32 mU/mL) was significantly higher than that from eyes with cataract (8.24+/-1.77 mU/mL, P=0.008). There was no significant difference between the serum EPO concentrations of POAG (26.46+/-10.36 mU/mL) and the control group (24.50+/-7.59 mU/mL, P=0.468). There was no correlation (P=0.165) between the EPO aqueous humor concentration and the EPO serum concentration while there was no correlation between the EPO aqueous humor concentration and the EPO serum concentration in the control group (P=0.819). CONCLUSIONS: The aqueous humor EPO level is increased in eyes with POAG.     

Higher concentration of transforming growth factor-beta in aqueous humor of glaucomatous eyes and diabetic eyes

PURPOSE: Diabetic retinopathy and glaucoma are the primary causes of acquired blindness. Cytokines including transforming growth factor (TGF)-beta may be involved in these diseases. We therefore collected aqueous humor samples from patients with glaucoma and/or diabetes who were undergoing surgery, and determined the concentration of TGF-beta. METHODS: Aqueous humor samples were collected from 80 patients (84 eyes), including 19 eyes with primary open-angle glaucoma (POAG), 22 eyes with diabetes, and 18 eyes with diabetes complicated with POAG. Twenty-five eyes with cataract served as controls. The concentration of TGF-beta1 or TGF-beta2 was measured by enzyme-linked immunosorbent assay. RESULTS: The concentration of TGF-beta1 was less than 0.1 pg/mL in all of the groups. In contrast to controls who had 1001.4 +/- 444.1 pg/mL, the concentration of total TGF-beta2 in the diabetes group was 1715.6 +/- 882.1 pg/mL, and that in the diabetes complicated with POAG group was 1692.9 +/- 361.9 pg/mL. These were significantly higher than that in controls. In contrast to the controls who had 321.2 +/- 197.9 pg/mL, the concentration of mature TGF-beta2 with POAG was 822.5 +/- 484.4 pg/mL, and that of diabetes complicated with POAG was 1058.9 +/- 648.4 pg/mL. These were significantly higher than that in the controls. The eyes with diabetes complicated with POAG also had a significantly higher concentration than the eyes with diabetes alone. CONCLUSION: Total TGF-beta2 and mature TGF-beta2 in high concentration may correlate with progression of POAG, diabetes, and diabetes complicated with POAG.     

Melatonin concentrations in aqueous humor of glaucoma patients

PURPOSE: To determine whether glaucoma patients exhibit an abnormal melatonin concentration in aqueous humor. DESIGN: Case-controlled study, laboratory investigation. METHODS: Aqueous humor and plasma samples of 28 patients with primary open-angle glaucoma and 31 nonglaucoma control patients were collected during surgery, and additional plasma samples were taken the night preceding surgery. Melatonin concentrations were determined using direct radioimmunoassay. RESULTS: This study shows detectable concentrations of melatonin in the aqueous humor of healthy humans (45% of subjects) and of glaucoma patients (36% of subjects) sampled in the morning, with similar levels of aqueous humor melatonin concentrations in both groups (6.4 +/- 9.3 standard deviation (SD) pg/ml and 3.6 +/- 1.9 pg/ml, respectively). We find no significant association between the severity of glaucoma and melatonin levels in aqueous humor or in plasma. CONCLUSIONS: Moderate and severe glaucoma does not appear to be associated with abnormal melatonin concentrations in aqueous humor, at least during the morning sampling period assayed in this study.     

血清及房水中IL-6水平与炎症性青光眼的相关性研究

目的:测定炎症相关性青光眼(简称炎症性青光眼)患者血清及房水中白细胞介素-6(IL-6)的水平,探讨IL-6在炎症性青光眼发生发展中的作用。方法:选取炎症性青光眼患者20例20眼作为试验组(A组),原发性慢性青光眼(原发性慢性开角型青光眼和原发性慢性闭角型青光眼)患者20例20眼作为高眼压对照组(B组),老年性白内障患者20例20眼作为正常对照组(C组)。采集三组患者血清及房水标本,通过电化学发光法分别检测血清与房水中IL-6的水平。结果:炎症性青光眼组、原发性慢性青光眼组、老年性白内障组血清IL-6水平分别为3.26±2.10,4.20±1.94,3.50±2.24pg/mL,差异无统计学意义(F=1.080,P=0.345)。炎症性青光眼组、原发性慢性青光眼组、老年性白内障组房水IL-6水平分别为293.77±38.72,135.27±32.72,115.80±29.97pg/mL,差异有统计学意义(F=164.86,P=0.000),炎症性青光眼组明显高于原发性慢性青光眼及老年性白内障组,差异有统计学意义(P<0.01;P<0.01),原发性慢性青光眼组与老年性白内障组相比,差异无统计学意义(P>0.05)。结论:炎症性青光眼患者房水IL-6水平的高表达与炎症反应密切相关,与高眼压状态无明显相关性。     

新生血管性青光眼患者房水和血浆中VEGF、TGF-β1和IL-6的测定及意义

背景 新生血管性青光眼(NVG)以虹膜和房角新生血管为主要特征,发病机制尚未完全阐明.研究证实多个细胞因子和炎性因子与新生血管的形成有关,但这些细胞因子与NVG的关系研究尚不完全清楚. 目的 探讨NVG患者房水和血浆中血管内皮生长因子(VEGF)、转化生长因子β1(TGF-p1)和白细胞介素-6(IL-6)质量浓度的变化及其意义.方法 采用前瞻性病例对照研究方法,纳入2014年5月至2015年3月于上海市东方医院确诊的NVG患者8例8眼、原发性开角型青光眼(POAG)患者10例10眼及年龄相关性白内障(ARC)患者10例10眼.眼部手术前1d收集患者空腹肘静脉血3～4 ml,离心后取上清液0.3～0.4 ml,于眼部手术时收集房水0.1 ～0.2 ml,采用ELISA法分别检测患者房水及血浆中VEGF、TGF-β1和IL-6质量浓度,对检测结果进行组间比较. 结果 NVG组患者房水和血浆中VEGF质量浓度分别为(2 769.85±390.88) pg/ml和(529.93±95.20) pg/ml,明显高于POAG组的(208.12±58.59) pg/ml和(219.28 ±24.44) pg/ml及ARC组的(158.88±12.35) pg/ml和(172.82±31.91) pg/ml,组间总体比较差异均有统计学意义(房水:F=433.80,P＜0.01;血浆:F=103.84,P＜0.01).NVG组患者房水和血浆中TGF-β1质量浓度分别为(157.94±113.00) pg/ml和(3 895.78±2 318.00) pg/ml,明显高于POAG组的(54.48±35.58) pg/ml和(2 196.13±1 185.39)pg/ml以及ARC组的(47.98±17.69) pg/ml和(1 937.28±933.27) pg/ml,组间总体比较差异有统计学意义(房水:F=7.88,P＜0.01;血浆:F=4.18,P＜0.05).NVG组房水和血浆中IL-6质量浓度分别为(234.87±41.64) pg/ml和(26.97±8.19) pg/ml,明显高于POAG组的(38.97±19.06) pg/ml和(19.54±5.11) pg/ml以及ARC组的(29.48±14.61) pg/ml和(18.50±3.57) pg/ml,组间总体比较差异均有统计学意义(房水:F=166.27,P＜0.01;血浆:F=5.59,P＜0.05). 结论 NVG患者房水及血浆中VEGF、TGF-β1、IL-6质量浓度明显高于POAG及ARC患者,提示3种细胞因子均参与NVG的发生及虹膜新生血管的形成,可能成为NVG治疗的靶点.     

Decreased levels of pigment epithelium-derived factor in eyes with neuroretinal dystrophic diseases

PURPOSE: To determine the concentration of pigment epithelium-derived factor (PEDF) in the aqueous humor of eyes with neuroretinal dystrophy. DESIGN: Observational case series. METHODS: Aqueous humor was obtained from patients during cataract surgery, and the PEDF concentration in the aqueous humor was measured by enzyme-linked immunosorbent assay. The primary diagnosis was cataract in 162 eyes; of these there were five eyes with retinitis pigmentosa, nine eyes with advanced glaucoma, and 148 eyes with cataract alone. RESULTS: The mean levels of PEDF in eyes with retinitis pigmentosa (0.24 +/- 0.04 microg/ml, mean +/- SE, P =.0004) and advanced glaucoma (0.46 +/- 0.08 microg/ml, P =.003) were significantly lower than that in eyes with cataract alone (0.86 +/- 0.04 microg/ml). CONCLUSION: The lower levels of PEDF in eyes with neuroretinal dystrophy may be related to the loss of the retinal ganglion cells or retinal pigment epithelium cells that synthesize PEDF.     

一氧化氮与青光眼患者眼压升高关系的研究

目的探讨一氧化氮(nitricoxide,NO)在青光眼患者眼压升高中的作用.方法对急性闭角型青光眼患者16例,老年性白内障患者29例,正常志愿者30例,应用高效液相色谱分析仪检测其血浆和房水中NO的含量,并以NO2和NO3之和表示.结果正常对照组血浆中NO的平均含量为(2969.37±862.85)ng/L;青光眼组血浆中NO的平均含量为(1390.78±302.95)ng/L,较对照组明显降低(t=2.853,P<0.01);白内障组血浆中NO的平均含量为(4234.89±1495.23)ng/L,较对照组明显升高.对照组房水中NO平均含量为(1405.83±602.70)ng/L;青光眼组房水中NO的平均含量为(2052.03±694.74)ng/L,与对照组比较差异无显著性(t=1.862,P＞0.05);白内障组房水中NO的平均含量为(2454.67±655.13)ng/L,较对照组明显升高.房水/血浆NO含量比值对照组为47.3%,白内障组为58.0%,二者的比值差异无显著性;而青光眼组为144.0%.结论血浆、房水中NO含量与急性闭角型青光眼眼压升高有关.     

Influence of argon laser trabeculoplasty on transforming growth factor-beta 2 concentration and bleb scarring following trabeculectomy

BACKGROUND: The purpose of this study was to evaluate the influence of previous argon laser trabeculoplasty (ALT) on transforming growth factor-beta 2 (TGF-beta 2) concentration of the aqueous humor and its influence on bleb scarring after trabeculectomy. METHODS: Fifty-one patients with primary open-angle glaucoma (POAG) and 29 patients with exfoliation (XFS) glaucoma were recruited for this prospective study before undergoing trabeculectomy. Sixty to 200 micro l of aqueous humor were analyzed for total and biologically active TGF-beta 2 concentrations (R and D Systems). TGF-beta 2 levels and a standardized bleb assessment were compared between the ALT- and non-ALT-treated groups. RESULTS: POAG eyes without ALT showed significantly higher total TGF-beta 2 levels (2,317.7+/-1,041.1 pg/ml) than eyes with previous ALT (1,621.6+/-899.6 pg/ml; P=0.026). No significant difference was found for active TGF-beta 2 levels (ALT: 238.1+/-119.0 pg/ml; no ALT: 220.1+/-96.9 pg/ml; P=0.585). In XFS patients ALT did not alter total TGF-beta 2 levels (ALT: 1,524.9+/-624.9 pg/ml, no ALT: 1,220+/-499.1 pg/ml; P=0.20), but active TGF-beta 2 was significantly higher in the ALT-treated (237.0+/-99.7 pg/ml) than in the non-ALT-treated (140.0+/-95.3 pg/ml, P=0.028) group. Bleb grading revealed no statistical difference between the ALT- and non-ALT-treated groups in POAG (P=0.545, Fisher's exact test), whereas XFS patients with ALT were at increased risk for scarring compared to non-ALT-treated patients (P=0.053). CONCLUSIONS: ALT appears to increase the risk of scarring in XFS patients because of increased levels of activated TGF-beta 2.     

The effect of previous surgery and topical eye drops for primary open-angle glaucoma on cytokine expression in aqueous humor

Purpose

To evaluate cytokine expression in the aqueous humor of patients with primary open-angle glaucoma (POAG) after previous glaucomatous and/or cataract surgery, and to determine the effect of intraocular pressure (IOP)-lowering eye drops on cytokine expression.

Methods

This prospective consecutive case study included 32 eyes diagnosed with POAG (19 with previous surgery and 13 without previous surgery, treated with topical antiglaucoma medication) and 12 eyes without signs of glaucoma. The Luminex 200 multiplex bead immunoassay was used to measure 27 cytokines in aqueous humor.

Results

Eyes suffering from POAG, with previous surgery, had significantly elevated concentrations of IL-6, IL-8, CCL2, CXCL9, and HGF, and a significantly lower concentration of CCL5, compared to POAG eyes without previous surgery, treated only with topical antiglaucoma medication. When compared with cataract controls, eyes with POAG and previous surgery had significantly elevated levels of G-CSF, IL-8, IL-12, CXCL10, and HGF, and significantly decreased concentrations of IL-17, CCL5, and VEGF in aqueous humor. In a comparison between POAG eyes without previous surgery and cataract controls, the cataract control eyes had significantly higher levels of IL-6 and CCL2, as the only significant difference.

Conclusions

POAG is associated with an aqueous inflammatory response in the aqueous humor, which is significantly elevated in eyes with previous surgery. In contrast, preoperative IOP-lowering eye drops did not significantly alter the anterior chamber milieu. The results of the current study indicate that filtration surgery has a higher success rate in eyes that have not experienced previous surgery.     

Endothelin 1 levels in the aqueous humor of dogs with glaucoma

PURPOSE: Endothelin 1 is a small peptide that is involved in regulation of intraocular pressure and modulation of ocular circulation. To investigate the role of endothelin 1 in canine glaucoma, the authors measured aqueous humor levels of endothelin 1 in healthy dogs and in dogs with hypertensive glaucoma. METHODS: Aqueous humor samples were obtained with general anesthesia from the eyes of healthy dogs (n = 5) and dogs with hypertensive glaucoma (n = 10). Measurements were made by enzyme immunoassay for endothelin 1. RESULTS: The endothelin 1 aqueous humor range was 1.12 - 3.63 pg/mL for healthy dogs and 1.97 - 14.97 pg/mL for glaucomatous dogs. The healthy and glaucomatous canine endothelin 1 aqueous levels (mean +/- SD) were 2.33 +/- 0.90 and 8.11 +/- 5.03 pg/mL, respectively. A two-way analysis of variance indicated that this difference was significant (P = 0.0084). The effect of age on endothelin 1 levels was not significant (P = 0.6283). The large variability found within the glaucomatous group could be explained by the degree of damage of the retina (P = 0.0006). There was no significant correlation between intraocular pressure and endothelin 1 aqueous humor levels within the glaucomatous group (P = 0.29). CONCLUSIONS: The aqueous humor of dogs with hypertensive glaucoma contains significantly higher levels of endothelin 1 than that of healthy dogs.     

Aqueous humor nitric oxide levels differ in patients with different types of glaucoma.

Nitric oxide (NO) has effects on the regulation of aqueous humor dynamics, but the exact mechanism is not yet established. To investigate the possible roles of NO in glaucoma, we determined NO levels in aqueous humor and plasma in glaucoma patients and a control group, cataract patients. The study is an open trial with purposed sampling. One hundred fifty-two patients, including 87 glaucoma patients and 65 cataract patients from two medical centers, were recruited. NO levels in the samples were measured by a chemiluminescence assay. We found that, although the mean aqueous humor NO level (mean +/- SEM) was higher in the glaucoma patients than in the cataract patients (39.7 +/- 1.5 microM vs. 35.5 +/- 1.3 microM, p < 0.05), NO levels varied significantly in different types of glaucoma. The juvenile glaucoma patients had the lowest mean NO level (8.4 +/- 0.9 microM), while the acute angle-closure glaucoma and neovascular glaucoma patients had the highest mean NO levels (64.8 +/- 7.6 microM, 67.3 +/- 8.2 microM). In comparison, the mean plasma NO level in the glaucoma patients was not statistically different from that in the cataract patients (14.1 +/- 1.2 microM vs. 13.9 +/- 1.1 microM, p = 0.91). Our data may provide information for applying NO-mimicking nitrovasodilators in the treatment of glaucoma.     

Preliminary clinical study on the management of angle-closure glaucoma by phacoemulsification with foldable posterior chamber intraocular lens implantation]

OBJECTIVE: To investigate the clinical results of phacoemulsification with foldable posterior chamber intraocular lens (PC-IOL) implantation in the management of angle-closure glaucoma with cataract. METHODS: Phacoemulsification with PC-IOL implantation performed on 47 eyes (42 cases) with angle-closure glaucoma and cataract was retrospectively studied, including 26 eyes with primary acute angle-closure glaucoma, 12 eyes with primary chronic angle-closure glaucoma, 5 eyes with secondary acute angle-closure glaucoma and 4 eyes with secondary chronic angle-closure glaucoma. RESULTS: After a mean postoperative follow-up of (18.40 +/- 9.51) months, the intraocular pressure was reduced from a preoperative mean of (25.47 +/- 18.43) mm Hg to a postoperative mean of (11.99 +/- 4.48) mm Hg (t = 4.918, P < 0.001). The mean anterior chamber depth was (1.69 +/- 0.46) mm preoperatively and (2.28 +/- 0.36) mm postoperatively (t = 7.738, P < 0.001). The best-corrected visual acuity was improved in 41 of 47 eyes (87.2%). CONCLUSION: Phacoemulsification with posterior chamber foldable intraocular lens implantation can be a good alternative in treating angle-closure glaucoma with cataract.     

Elevated homocysteine levels in aqueous humor of patients with pseudoexfoliation glaucoma

PURPOSE: To determine total homocysteine levels in aqueous humor of pseudoexfoliation open-angle glaucoma patients. DESIGN: Case-control study. METHODS: Total homocysteine levels were measured by enzyme-linked immunosorbent assay in aqueous humor and plasma of 29 patients with pseudoexfoliation glaucoma and 31 control patients with cataract. Patients with factors affecting homocysteine levels were excluded. RESULTS: We observed significantly elevated (twofold) homocysteine levels in the aqueous humor of the glaucoma patients (Z = -5.11, P <.0001). Additionally, the calculated ratio (plasma:aqueous humor) was significantly lower in these patients (Z = -3.57, P <.001), and aqueous homocysteine was significantly correlated with their respective elevated plasma levels (r =.42, P =.02). CONCLUSIONS: Because homocysteine induces vascular injury and alterations of extracellular matrix, high aqueous homocysteine may trigger the abnormal matrix accumulation characteristic. It may reflect the proposed impairment of the blood-aqueous barrier of pseudoexfoliation open-angle glaucoma and be involved in its pathogenesis.     

前部视网膜冷凝术对新生血管性青光眼患者房水中血管内皮生长因子含量的影响

目的 探讨前部视网膜冷凝术对新生血管性青光眼患者房水中血管内皮生长因子（VEGF）含量的影响以及VEGF含量的变化与虹膜新生血管之间的关系。方法对28例确诊为新生血管性青光眼患者行虹膜血管造影,确定新生血管的范围和数量后,行前部视网膜冷凝术,7～14d后经虹膜血管造影确定虹膜新生血管大部分消退后,再行小梁切除术。分别于前部视网膜冷凝术前和小梁切除术前抽取房水标本,另取30例老年性白内障患者房水标本。采用酶联免疫吸附法分别测定全部房水标本中的VEGF含量。结果小梁切除术前房水中VEGF的含量[（2．096±0．512）ng／ml]明显低于前视网膜冷凝术前房水中VEGF含量[（0．478±0．312）ng／ml],两者比较差异有统计学意义（P〈0．01）。小梁切除术前房水中VEGF含量明显高于老年性白内障患者房水中VEGF的含量[（0．198±0．045）ng／ml],两者比较差异有统计学意义（P〈0．01）。结论VEGF在虹膜新生血管的形成中可能发挥一定的作用;阻断促使虹膜产生新生血管的VEGF来源,可抑制新生血管性青光眼的发生.（中华眼科杂志．2007．43：622-625）     

Increased levels of transforming growth factor-betal and -beta2 in the aqueous humor of patients with neovascular glaucoma.

BACKGROUND AND OBJECTIVE: To measure the concentrations of transforming growth factor-betal and beta2 (TGF-beta1 and TGF-beta2) in the aqueous humor of patients with neovascular glaucoma (NVG). PATIENTS AND METHODS: Patients were divided into four groups: NVG secondary to central retinal vein occlusion (group 1), NVG secondary to proliferative diabetic retinopathy (group 2), central retinal vein occlusion without rubeosis (group 3), and senile cataract (group 4). The total TGF-beta 1 and TGF-beta2 concentrations in the aqueous humor of the four groups were measured by enzyme linked immunosorbent assay. RESULTS: The mean concentrations of total TGF-betal were 600.7 +/-436.7 microg/mL in group 1, 802.0 +/-359.5 pg/mL in group 2, and undetectable in groups 3 and group 4 (P < .05). The mean concentrations of total TGF-beta2 were 6,307.9+/- 2,206.2 microg/mL in group 1, 5,908.0+/-2,033.2 microg/mL in group 2, 899.7+/- 425.6 microg/mL in group 3, and 385.7 +/-89.9 microg/mL in group 4. The total TGF-betal and TGF-beta2 concentrations in groups 1 and 2 were significantly higher than those in groups 3 and 4, whereas the total TGF-beta2 concentration in group 3 was significantly higher than that in group 4 (P < .05). There was no significant difference in the TGF-betal or TGF-beta2 concentrations between groups 1 and 2 (P> .05). CONCLUSIONS: The abnormally high concentrations of TGF-betal and TGF-beta2 in the aqueous humor of patients with NVG may explain some aspects of the pathogenesis of NVG and the high failure rate of filtering operations in NVG.     

Significant variation of the elevated nitric oxide levels in aqueous humor from patients with different types of glaucoma

Though several studies have shown that the biochemical function of nitric oxide (NO) in the eye might play an important role in the regulation of intraocular pressure (IOP), local control of ocular blood flow and loss of retinal ganglion cells by apoptosis, it is unclear whether the role of NO is similar in the pathogenesis of different kinds of glaucoma: primary open-angle glaucoma (POAG), chronic closed-angle glaucoma (CCAG) and neovascular glaucoma (NVG). To further explore this issue, we measured the concentrations of NO in aqueous humor and plasma samples from patients with POAG (n = 31), CCAG (n = 76), NVG (n = 8) and cataract (n = 30). All of the NVG patients suffered from severe proliferative diabetic retinopathy, while other patients were free of any other systemic disease. The NO levels in both aqueous humor and plasma samples were assessed by chemiluminescence assay. We found that the NO levels in aqueous humor samples were greatly varied in patients with POAG (36.2 +/- 3.3 microM), CCAG (47.7 +/- 3.4 microM) and NVG (65.8 +/- 5.4 microM), and all of them were significantly higher than in cataract patients (27.0 +/- 2.9 microM p < 0.05). Except NVG patients whose NO levels in plasma samples were highest (24.1 +/- 3.5 microM) among all groups, the plasma NO levels were not significantly different between the other glaucoma patients and the cataract patients. We therefore concluded that significant variation of the elevated NO levels in aqueous humor samples from the patients with different types of glaucoma may reflect their differences in the pathogenesis.     

青光眼患者血清及房水一氧化氮浓度的测定

目的 测定青光眼患者血清及房水一氧化氮(NO)浓度并探讨其在青光眼发病中的作用。方法 实验患者分为青光眼组和白内障组,应用硝酸还原酶法分别测定两组患者血清及房水NO浓度。结果 两组患者血清NO浓度无显著性差异,青光眼组内各类型之间血清NO浓度亦无显著性差异。原发性开角型青光眼患者房水NO浓度较对照组及其他类型青光眼显著降低,闭角型青光眼患者房水NO浓度较对照组显著升高(P<0.01)。 结论 眼压升高可引起房水NO浓度升高,过多的NO可损伤小梁网及邻近的葡萄膜及视网膜组织。开角型青光眼患者由于房角原生型一氧化氮合成酶的减少引起房水NO浓度的降低,此可能为眼压升高的原因之一。     

Decreased nitric oxide production in primary open-angle glaucoma

PURPOSE: Raised intraocular pressure (IOP) is the major risk factor responsible for optic nerve damage in primary open-angle glaucoma (POAG). The trabecularmeshwork acts as a valve in aqueous outflow and relaxes with nitric oxide (NO) agonists. Since NO is synthesized by endothelium and smooth muscle elsewhere in the body, this study investigated the NO levels in the aqueous humor of patients with POAG compared with cataract patients. MATERIALS AND METHODS: Aqueous humor samples were taken by paracentesis from 16 consecutive patients with POAG (9 male and 7 female; mean age 69.0+/-3.4 yrs) and 14 age and sex-matched controls with cataract (8 male and 6 female; mean age 66.7+/-4.1 yrs) during elective surgery. As an indicator for NO, aqueous total nitrite levels (end - product of NO) were measured by Greiss reaction. The Mann-Whitney U test was used for statistical analysis and P <0.05 was considered significant. RESULTS: The mean age and sex in two groups were comparable. The mean aqueous humor NO levels were significantly (P = 0.001) lower in patients with glaucoma (72.72+/-11.21 micromol/L) than in patients with cataract and no glaucoma (86.92+/-11.23 micromol/L). CONCLUSIONS: Decreased NO production in patients with POAG indicates that NO-producing cells may be lost as the disease progresses. The control of NO levels in the eye might be a therapeutic target in glaucoma.