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.     

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.     

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.     

Characteristic Profiles of Inflammatory Cytokines in the Aqueous Humor of Glaucomatous Eyes

Purpose: To analyze cytokine profiles of the aqueous humor of eyes with primary open-angle glaucoma (POAG), neovascular glaucoma (NVG), and cataract (as controls).

Methods: A multiplex bead assay was used to measure concentrations of 27 cytokines in aqueous humor samples from 54 eyes.

Results: Detection rates were as follows: IL-7: NVG higher than POAG; IL-10: POAG lower than cataract or NVG; and GM-CSF: cataract higher than POAG or NVG. Concentrations were as follows: IL-8, IP-10, MCP-1, and MIP-1β: POAG and NVG higher than cataract; IL-9: POAG lower than NVG; IL-12: POAG lower than cataract or NVG; and VEGF: NVG higher than cataract or POAG and POAG lower than cataract. Further analysis showed that IL-8, IP-10, MCP-1, and MIP-1β were correlated with intraocular pressure and age.

Conclusions: The detection rates and levels of various cytokines had different patterns in POAG and NVG patients, suggesting distinctive alterations in the microenvironment in different types of glaucoma.     

Transforming growth factor β2 levels in the aqueous humor in different types of glaucoma and the relation to filtering bleb development

PURPOSE: To investigate the transforming growth factor beta 2 (TGF-beta 2) levels and total protein levels in the aqueous humor of eyes with different types of glaucoma [primary open-angle glaucoma (POAG), pseudoexfoliation glaucoma (PSX), juvenile glaucoma (JG)], and the relation to filtering bleb development after trabeculectomy. METHODS: Aqueous humor was collected at the beginning of surgery from 52 eyes with glaucoma (29 POAG eyes, 17 PSX eyes, 6 JG eyes) and from 29 control eyes that underwent cataract operation. TGF-beta 2 levels (intrinsically activated and total TGF-beta 2) using ELISA methods as well as total protein concentrations of the aqueous humor were determined. All preoperative clinical data of the glaucoma eyes (age, gender, IOP, previous treatment, type of surgery) were compared with the TGF-beta 2 levels. In 40 of these eyes, the postoperative follow-up (filtering bleb development, need for intervention, IOP) was correlated to the preoperatively determined TGF-beta 2 levels. RESULTS: TGF-beta 2 levels were increased in nearly half of the eyes with POAG and in most of the eyes with JG, but in eyes with PSX, TGF-beta 2 levels were within the normal range. No correlation between TGF-beta 2 levels and age, gender, IOP, previous treatment, or type of surgery, or between TGF-beta 2 levels and protein levels in aqueous humor, was found. Correlation between bleb formation and TGF-beta 2 levels revealed that all but two of the POAG eyes with good clinical outcome (type 1 bleb) had normal levels of activated TGF-beta 2. Of the 13 eyes that needed postoperative intervention (type 2 and type 3 bleb), 8 had high and 5 had normal TGF-beta 2 levels. CONCLUSIONS: PSX eyes differ from POAG and JG eyes not only by their clinical or biomicroscopic appearance, but also by their normal TGF-beta 2 levels in aqueous humor. The fact that most of the POAG eyes with favorable bleb development had normal TGF-beta 2 levels indicated that there might be some relationship between bleb formation and TGF-beta 2 levels. On the other hand, the fact that eyes with less favorable bleb development had both low and high TGF-beta 2 levels indicated that other factors are also involved in the scarring of the filtration bleb.     

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.     

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.     

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.     

GDxVCC检测原发性开角型与可疑青光眼视网膜神经纤维层损害的对比研究

目的采用GDxVCC系统检测正常人、可疑开角型青光眼(suspected open angle glaucoma，SOAG)以及原发性开角型青光眼(primary open angle glaucoma，POAG)患者的视盘周围视网膜神经纤维层(retinal nerve fiber layer，RNFL)厚度，并进行对比分析，探讨GDxVCC系统在青光眼早期诊断中的价值。设计前瞻性对照研究。研究对象42例SOAG，36例POAG以及年龄相匹配的36例正常人参加此项研究。方法所有参加者进行视野与GDxVCC系统检查，选择一眼进行分析。采用方差分析，对SOAG、POAG、正常人的RNFL参数进行两两比较。主要指标GDxVCC检测RNFL厚度。结果POAG组与正常组问所有RNFL参数差异均有极显著意义(P=0．000)；POAG组与SOAG组间所有RNFL参数差异均有极显著意义(P=0．000)；SOAG组与正常组间椭圆平均值差异无统计学意义(P=0．234)，但其上方平均值与下方平均值及神经纤维指数差异均有统计学意义(P=0．044、P=0．045、P=0．035)，TSNIT标准差有极显著意义(P=0．000)。结论GDxVCC系统能更早地发现青光眼性RNFL结构损害，不仅可用于青光眼诊断和随访，亦可用于对可疑青光眼进行追踪。     

The Aqueous Levels of TGF-β2 in Patients with Glaucoma

PURPOSE: To evaluate the aqueous levels of transforming growth factor beta-2 (TGF-beta2) in open angle glaucoma patients. METHODS: The aqueous levels of active TGF-beta2 were detected in 17 eyes of 17 patients using ELISA method. The control group consisted of 6 cataract extracted patients. RESULTS: Mean age of the patients (60.8 +/- 8.8 years) was similar to that of the controls (57.5 +/- 9.8 years) (p = 0.516). Levels of TGF-beta2 in aqueous samples of glaucoma patients (2.74+/- 1.23 ng/ml) were found to be elevated when compared to those of controls (1.67 +/- 0.32 ng/ml) (p = 0.020). CONCLUSION: We might suggest that the elevated levels of TGF-beta2 in the aqueous of glaucoma patients could play a role in the pathogenesis of glaucoma.     

Quantitative and qualitative analyses of transferrin in aqueous humor from patients with primary and secondary glaucomas.

By using a highly sensitive and specific radioimmunoassay and the slot-blot technique, transferrin was quantified in fresh samples of aqueous humor from patients with primary open-angle glaucoma (POAG, n = 36) or secondary glaucoma (SG, n = 18). The levels were compared with those in aqueous humor obtained from age-matched patients without glaucoma (n = 33) and in primary and secondary aqueous humor from normal dogs (n = 10) in which breakdown of the blood-aqueous barrier was induced experimentally. The concentration of transferrin in the aqueous humor of human control subjects ranged from 0.3-3.4 mg/dl (mean +/- standard deviation, 1.36 +/- 0.66 mg/dl); in POAG samples, from 0.34 to greater than 10 mg/dl (2.07 +/- 1.90 mg/dl); and in SG samples, from 0.29 to greater than 10 mg/dl (2.79 +/- 2.24 mg/dl). The level of transferrin in secondary aqueous humor samples obtained from dogs was as much as ninefold greater than that in primary aqueous humor. The protein concentration in the human aqueous humor samples was 11.87 +/- 4.47 mg/dl for control subjects, 62.11 +/- 56.74 mg/dl for patients with POAG, and 124.53 +/- 152.67 mg/dl for those with SG. In dogs, the protein levels were 7.97 +/- 3.12 mg/dl for primary aqueous humor and 191.9 +/- 149.8 mg/dl for secondary aqueous humor. A significant correlation (r = 0.744, P less than 0.01) was found between total protein and transferrin contents in the samples of aqueous humor from patients with glaucoma but not in the samples from age-matched control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

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。     

Oxidant/antioxidant balance in the aqueous humor of patients with glaucoma

AIM: To evaluate total antioxidant status (TAS), total oxidant status (TOS), and the oxidative stress index (OSI) of the aqueous humor (AH) in patients with glaucoma. METHODS: The prospective study was composed of a study group (n=31) and a control group (n=31). Fifteen patients in the study group were diagnosed with primary open angle glaucoma (POAG), and 16 patients were diagnosed with pseudoexfoliation glaucoma (PEG). The control group was composed of non-glaucomatous patients with cataracts. AH samples were collected and analyzed for TAS, TOS, and OSI levels. RESULTS: Mean AH TAS level was significantly higher in patients with glaucoma than that in the control group (P<0.01). Mean TOS and OSI levels tended to increase in patients with glaucoma. No significant differences in TAS, TOS, or OSI levels were observed between patients with POAG and PEG. CONCLUSION: High levels of TAS were observed in patients with glaucoma, which was likely a response to the increased oxidative stress observed in these patients.     

雷珠单抗对房水中炎症相关细胞因子含量的影响

目的:比较新生血管性青光眼(neovascular glaucoma,NVG)与年龄相关性白内障患者房水中炎症相关细胞因子浓度,观察玻璃体腔内注射雷珠单抗前后房水中炎症相关细胞因子表达变化.方法:纳入21例21眼NVG患者以及20例20眼年龄相关性白内障患者作为对照.NVG患者先予玻璃体腔内注射雷珠单抗,再行青光眼房水引流阀植入术.在玻璃体腔内注射雷珠单抗以及2~7d后行青光眼房水引流阀植入术术前抽取NVG患者房水,同时在白内障手术时抽取年龄相关性白内障患者房水.用Multiplex微珠免疫分析系统检测房水中细胞因子浓度.结果:NVG组患者玻璃体腔内注射雷珠单抗前房水中IL-1β,IL-6,IL-8,MCP-1以及VEGF浓度明显高于年龄相关性白内障患者,差异均有统计学意义(均P<0.001).玻璃体腔内注射雷珠单抗后,NVG患者房水中IL-6,IL-8,MCP-1以及VEGF浓度较注射雷珠单抗前明显降低,差异有统计学意义(P<0.05).NVG患者房水中检测的炎症相关细胞因子的浓度与患者年龄、术前眼压均无明显相关性.结论:NVG患者玻璃体腔内注射雷珠单抗前房水中与炎症相关的细胞因子表达明显上调.NVG患者行雷珠单抗治疗后,房水中与炎症相关的细胞因子明显下调.     

Effects of TGF-beta2 in perfused human eyes

PURPOSE: TGF-beta2 is known to be present at elevated levels in the aqueous humor of patients with primary open-angle glaucoma (POAG). Studies have shown that TGF-beta2 influences cultured trabecular meshwork (TM) cells, but the effects of this cytokine on intact TM and outflow facility have not been studied. The purpose of this study was to investigate whether TGF-beta2 treatment induces changes in outflow facility and morphologic changes in the TM tissue and whether these changes are comparable to those previously recorded in glaucomatous eyes. METHODS: Baseline facility was measured in paired human eyes (n = 8 pairs), with a constant-flow anterior segment culture system. Medium perfusing experimental eyes was then supplemented with activated human recombinant TGF-beta2 (3.0 ng/mL, comparable to or slightly greater than measured aqueous humor levels in patients with POAG), and facility was measured for at least 8 days. At the conclusion of the perfusion, eyes were fixed and processed for light microscopy, transmission electron microscopy, and immunolabeling studies. RESULTS: TGF-beta2 perfusion reduced outflow facility by 27% (P = 0.03) and promoted focal accumulation of fine fibrillar extracellular material in multilayered structures under the inner wall of Schlemm's canal. In treated eyes, Schlemm's canal was 27% shorter (P = 0.02), and the length of the inner wall apparently available for fluid flow was 33% less (P = 0.001), both compared with paired control eyes. CONCLUSIONS: TGF-beta2 reduces outflow facility when perfused into cultured human anterior segments. Furthermore, TGF-beta2 affects the extracellular matrix of the trabecular meshwork in a manner that is consistent with the observed reduction in outflow facility. Although the distribution of accumulated fibrillar material was different in these perfused eyes than that in POAG, the difference could be due to variation in biomechanical environment for TM cells in cultured anterior segments compared with the living eye. Overall, these results support the hypothesis that elevated TGF-beta2 levels in the aqueous humor play a role in the pathogenesis of the ocular hypertension in POAG.     

The relationship between gelatinase A activity in aqueous humor and glaucoma

PURPOSE: To investigate whether abnormal expression of gelatinase A in aqueous humor may be related to the development of glaucoma, the activity of gelatinase A in aqueous humor of patients with glaucoma and patients with cataract was measured and compared. METHODS: Six primary patients with open-angle glaucoma (POAG), four patients with chronic angle closure glaucoma (CACG), four patients with normal tension glaucoma (NTG), and 14 patients with cataract were enrolled. The aqueous humor of each patient was collected during surgery, and total protein concentration and gelatinase activity in the aqueous humor were measured by protein assay kit and zymography, respectively. RESULTS: In patients with POAG, total protein concentration doubled and gelatinase A activity increased by 3.9 times compared with patients with cataract. However, there were no statistically significant differences in total protein concentration and gelatinase A activity in patients with CACG or NTG compared with patients with cataract. CONCLUSION: The development of POAG may be associated with the abnormal expression of gelatinase A in aqueous humor.     

Matrix metalloproteinases and their inhibitors in aqueous humor of patients with pseudoexfoliation syndrome/glaucoma and primary open-angle glaucoma

PURPOSE: To determine the presence, activity, and quantitative differences of matrix metalloproteinases (MMPs) and their endogenous inhibitors (TIMPs) in aqueous humor and serum samples of patients with pseudoexfoliation (PEX) syndrome, PEX glaucoma (PEXG), primary open-angle glaucoma (POAG), and cataract. METHODS: Aqueous humor and serum samples were collected from 100 patients with PEX syndrome, PEX glaucoma (PEXG), POAG, and cataract, respectively. Levels of MMP-1, -2, -3, -7, -9, and -12 and TIMP-1 and -2 were determined by zymography, Western blot analysis, and specific immunoassays. Activity assay kits were used to quantitate levels of endogenously activated MMP-2 and -9. RESULTS: MMP-2, -3, -7, -9, and -12 and TIMP-1 and -2 were identified in human aqueous humor samples from all groups of patients with a six to sevenfold molar excess of TIMPs over MMPs. Whereas serum samples showed no significant differences, total MMP-2 and -3 and TIMP-1 and -2 were detected at significantly higher concentrations in aqueous samples from PEX eyes with and without glaucoma compared with cataractous eyes. MMP-2 and -3 and TIMP-1 were also detected in higher, but not significantly different, amounts in aqueous samples of POAG eyes. However, levels of endogenously activated MMP-2 were significantly decreased in both PEX and POAG samples. The ratio of MMP-2 to its principal inhibitor TIMP-2 was balanced in cataract samples, but was decreased in samples from patients with PEXG, resulting in an excess of TIMP-2 over MMP-2. CONCLUSIONS: The findings suggest that complex changes in the local MMP-TIMP balance and reduced MMP activity in aqueous humor may promote the abnormal matrix accumulation characteristic of PEX syndrome and may be causally involved in the pathogenesis of both PEX glaucoma and POAG.     

原发性开角型青光眼早期诊断中视网膜电图和蓝黄视野检查联合应用研究

目的:研究图形视网膜电图(pattern electroretinogram,PERG)和蓝黄视野(blue-on-yellow perimetry,B/YP)在原发性开角型青光眼(primary open angle glaucoma,POAG)早期诊断方面的临床应用价值。方法:通过对25例42眼标准自动视野检查正常的可疑开角型青光眼(SOAG)患者和25例50眼正常人PERG的P50,N95波的振幅、峰时值和B/YP的视野结果进行对比分析。结果:在SOAG患者中,PERG检查19例34眼的P50,N95波振幅下降,峰时延长,B/YP检查18例32眼视野出现异常,与正常人比较,有显著性差异(P<0.01)。结论:SOAG患者PERG和B/YP的异常结果表明其视网膜神经节细胞已经受损,两者联合应用是POAG早期诊断的有效途径。     

开角型青光眼视盘周围脉络膜萎缩与视野缺损的相关性研究

目的:探讨原发性开角型青光眼(primaryopenangleglaucoma,POAG)和可疑开角型青光眼(suspectedopenangleglaucoma,SOAG)视盘周围脉络膜萎缩(peripapillarychoroidalatrophy,PPCA)的发生率及不同分区的面积大小与视野指数平均缺损(Meandefect,MD)之间的相关性。方法:对128只POAG和78只SOAG行静态视野检查及眼底视盘彩色照相,对有PPCA改变的视盘确定其α区和(或)β区,并测出不同分区的面积。结果:POAG组中,PPCA的α和β区的发生率分别为57.03%和39.84%,面积均数分别为(0.54±0.37)mm2和(1.68±1.06)mm2,MD为(8.31±3.66)dB;SOAG组中,α和β区的发生率分别为43.59%和26.92%,面积均数分别为(0.42±0.29)mm2和(1.15±0.67)mm2,MD则为(4.16±2.07)dB。在2组病例中,α区和β区面积值与MD之间均具有显著意义的正性相关(P<0.001)。结论:PPCA不同分区的面积值与MD之间具有显著相关性;β区的发展是辨认青光眼或青光眼性视神经损害是否进展的重要参数,有助于发现及预测青光眼病情的发展。     

原发性开角型青光眼患者房水中IL-37和IL-6的表达及意义

目的:检测原发性开角型青光眼(POAG)患者房水中IL-37和IL-6的含量,并分析IL-6和IL-37含量与眼压或视野平均缺损的相关性。方法:采用前瞻性病例对照研究,利用酶联免疫吸附试验(ELISA)对2019-06/2020-01在南京医科大学附属眼科医院连续就诊的25例POAG患者和25例年龄相关性白内障(ARC)患者房水中IL-37和IL-6含量进行检测。同时测定POAG组患者眼压、视野平均缺损。结果:房水中IL-37和IL-6含量POAG组患者为25.80±2.87、43.87±7.75pg/mL,ARC组患者为23.75±3.88、36.53±7.60pg/mL,两组间IL-37和IL-6含量比较均有差异(P<0.05)。IL-6与眼压正相关(r=0.5817,P<0.05),IL-37与视野缺损正相关(r=0.4520,P<0.05)。结论:POAG患者房水中IL-37、IL-6含量均显著高于ARC组。IL-37和IL-6介导的免疫炎症反应可能参与了POAG的发病机制。