眼内液中PEDF、VEGF含量变化对糖尿病视网膜病变的意义

目的:测定增殖型糖尿病视网膜病变(PDR)患者房水、玻璃体及血清中色素上皮源性因子(PEDF)、血管内皮生长因子(VEGF)的浓度变化,并探讨其变化的来源及临床意义.方法:以41只糖尿病视网膜病变患眼为研究对象,其中16只继发虹膜新生血管(NVI),21只特发性黄斑裂孔(MH)患眼作为对照.应用酶联免疫吸附法(ELISA),分别测定3组患眼房水、玻璃体、血清中PEDF、VEGF的质量浓度.采用单因素方差分析比较3组房水、玻璃体、血清中PEDF及VEGF的水平,采用Pearson相关性检验分析房水中PEDF、VEGF水平与血清、玻璃体中的关系,并分别分析3种眼内液中PEDF与VEGF的关系.结果:房水中PEDF浓度在对照组、PDR无继发NVI组、PDR继发NVI组依次降低,VEGF浓度依次升高,玻璃体中PEDF、VEGF浓度具有类似的变化趋势.房水PEDF、VEGF水平与血清的无明显相关性,与玻璃体的呈一定正相关性.眼内液中PEDF浓度与VEGF浓度呈负相关.结论:眼内液PEDF水平降低、VEGF水平升高可能对PDR的发生、发展起到重要作用.PDR发展过程中,房水中这两种因子的浓度变化可能主要受眼局部病变影响.PEDF、VEGF分别作为血管抑制因子和血管刺激因子的代表,其眼内分布失衡可能是促成NVI及视网膜新生血管发生的重要因素.     

Vitreous levels of pigment epithelium-derived factor and vascular endothelial growth factor: implications for ocular angiogenesis

PURPOSE: Pigment epithelium-derived factor (PEDF) has been demonstrated to suppress ocular angiogenesis in several animal models. In this study, we sought to measure the levels of PEDF and vascular endothelial growth factor (VEGF) in the vitreous of patients with and without ocular neovascular disorders. DESIGN: Case-control study of patients undergoing intraocular surgery for a variety of neovascular and nonneovascular conditions. METHODS: Vitreous samples were collected from 65 eyes of 65 patients with no neovascular disorder (n = 24), choroidal neovascularization (n = 9), active proliferative diabetic retinopathy (n = 16), and inactive proliferative diabetic retinopathy (n = 16). The levels of VEGF and PEDF in these vitreous samples were determined by enzyme-linked immunosorbent assay. RESULTS: The VEGF levels were at or below the level of detectability in the reference and choroidal neovascularization groups. The VEGF levels were significantly elevated in both the active and inactive PDR groups, and significantly higher in the active PDR group as compared with the inactive PDR group. The PEDF levels, which were present at relatively high concentrations in all groups, were higher in patients with active PDR compared with the control and choroidal neovascularization groups. CONCLUSIONS: High levels of immunoreactive PEDF are present in the vitreous of individuals with or without ocular neovascularization, but PEDF levels are significantly higher in patients with active PDR compared with patients with choroidal neovascularization or nonneovascular retinal diseases. Although these results do not preclude the possibility that endogenous PEDF helps to modulate ocular neovascularization, they do not support ischemia-induced downregulation of PEDF as a mechanism for such modulation.     

Levels of vascular endothelial growth factor and pigment epithelium-derived factor in eyes before and after intravitreal injection of bevacizumab

Purpose  Bevacizumab is a human monoclonal IgG1 antibody that blocks the action of vascular endothelial growth factor (VEGF). The purpose of this study was to determine the level of VEGF and pigment epithelium-derived factor (PEDF) in eyes with proliferative diabetic retinopathy (PDR) before and after an intravitreal injection of bevacizumab. Methods  Eleven eyes of ten patients were studied. Patients were included if they had neovascular glaucoma, rubeosis of the iris with PDR, or aggressive PDR. Samples of aqueous humor were collected just before the injection of bevacizumab and the vitrectomy. The concentrations of VEGF and PEDF in the aqueous humor were measured by enzyme-linked immunosorbent assay, and the effects of bevacizumab on PDR were evaluated. Results  The free VEGF concentration before the injection was 676.5 ± 186.7 pg/ml (mean ± SEM, n = 11). Seven days later, it was significantly reduced to 7.1 ± 7.1 pg/ml (P < 0.005, n = 9). The PEDF concentration before the injection was 2.32 ± 0.49 μg/ml (n = 11), and 7 days later, it was 3.23 ± 0.76 μg/ml (P = 0.33). During the vitrectomy, patients had less intraoperative bleeding when the neovascular tissues were cut. Conclusions  An intravitreal injection of bevacizumab significantly decreased the free VEGF in the aqueous humor by 7 days, indicating that the clinical effects of bevacizumab appear rapidly. However, intravitreal bevacizumab did not affect the level of intraocular PEDF.     

VEGF在PDR中的表达及作用的研究

目的:研究增殖性糖尿病视网膜病变(proliferative diabetic retinopathy,PDR)患者血液、房水、玻璃体中血管内皮生长因子(vascular endothelial growth factor,VEGF)含量的变化,探讨VEGF与PDR的关系,为抗VEGF药物治疗的给药途径及剂量等提供理论依据。方法:采用双抗体夹心酶联免疫吸附测定法定量检测无糖尿病视网膜病变(NDR)组,单纯性糖尿病视网膜病变(BDR)组,增殖性糖尿病视网膜病变(PDR)组患者和正常对照组血浆中VEGF含量,还检测PDR患者房水、玻璃体中和正常对照组房水、玻璃体中VEGF含量,并进行综合分析。试剂盒购自美国R&D公司,其质量和灵敏度相对较高。结果:PDR组房水中VEGF含量有增高趋势,但与正常对照组比较,无统计学差异(P>0.05)。PDR患者玻璃体中VEGF含量明显增高,与正常对照组比较差异非常显著(P<0.01)。PDR组自身血浆、房水、玻璃体中VEGF含量比较有逐渐增高趋势,三者之间有显著性差异(P<0.01)。正常对照组血浆、房水、玻璃体中VEGF含量三者之间无显著性差异(P>0.05)。血浆VEGF含量在正常对照组中最高,而玻璃体中VEGF含量在PDR患者中最高。结论:PDR患者眼内尤其是玻璃体中VEGF含量大幅度增高,可能对促进DR发展恶化起了关键性的作用。在正常人,VEGF更多地存在于血浆中发挥其生物学效应。在严重DR患者中,玻璃体中异常地出现大量VEGF,推测来自缺血缺氧的视网膜,并可能有向眼前段扩散的趋势。     

增殖性糖尿病视网膜病变玻璃体中PEDF的定量分析

目的:定量测定色素上皮细胞衍生因子(PEDF)在增殖性糖尿病视网膜病变(PDR))患者玻璃体中的质量浓度,探讨其在PDR发病机制中的作用。方法:采用双抗体夹心酶联免疫吸附测定法定量检测26例PDR、5例NPDR及7例对照组患者玻璃体中PEDF的质量浓度。结果:PDR组玻璃体中PEDF质量浓度小于对照组(P<0.05)及NPDR组(P<0.01)。PDR组中Ⅵ期患者玻璃体中PEDF质量浓度小于IV期(P<0.05)及V期(P<0.05)。结论:PDR患者玻璃体中PEDF降低,PEDF降低可能与视网膜新生血管的形成有关,其在PDR发展过程中起着重要作用。     

Increased levels of vascular endothelial growth factor in the aqueous humor of patients with diabetic retinopathy

Purpose:

This study aims to investigate the levels of aqueous vascular endothelial growth factor (VEGF) in diabetic patient groups in comparison to normal subjects, and to correlate elevated VEGF with the severity of diabetic retinopathy (DR).

Materials and Methods:

Aqueous samples were obtained from 78 eyes of 74 patients undergoing intraocular surgery and they were examined by the enzyme-linked immunosorbent assay. Color photographs, optical coherence tomography scans, and fluorescein angiography were used to evaluate patients preoperatively.

Results:

A strong statistical correlation was found to exist between the level of aqueous VEGF and the severity of DR (P < 0.001), whereas, the VEGF levels in a control group and a diabetic group without DR were not significantly different (P = 0.985). Aqueous VEGF levels were significantly elevated in patients with proliferative DR (PDR) as compared to the control group (P < 0.001), to diabetic patients without retinopathy (NDR) (P < 0.001), and to diabetic patients with nonproliferative DR (NPDR) (P < 0.001). The aqueous VEGF levels were significantly higher in patients with active PDR than in those with quiescent PDR (P = 0.001). On the other hand, a statistically insignificant (P = 0.065) correlation was found between elevated aqueous VEGF and the presence of macular edema in the NPDR group.

Conclusions:

VEGF was elevated in the aqueous humor of patients with DR compared to that in normal eyes. The aqueous VEGF level had a strong correlation with the severity of retinopathy along with a statistically insignificant difference in macular edema.     

Unbalanced vitreous levels of pigment epithelium-derived factor and vascular endothelial growth factor in diabetic retinopathy

PURPOSE: To determine the levels of pigment epithelium-derived factor (PEDF) and vascular endothelial growth factor (VEGF) in the vitreous of patients with diabetic retinopathy (DR). DESIGN: Experimental study of PEDF and VEGF levels in vitreous samples collected during vitrectomy. METHODS: The levels of PEDF and VEGF were measured by enzyme-linked immunosorbent assay in the vitreous of 46 eyes of 43 patients who underwent vitrectomy with diabetic retinopathy (DR) (32 eyes of 29 patients) and an idiopathic macular hole (MH) (14 eyes of 14 patients). RESULTS: The vitreal concentration of PEDF was significantly lower at 1.11 +/- 0.14 microg/ml (mean +/- standard error) in eyes with DR than in eyes with MH at 1.71 +/- 0.22 microg/ml (P =.021). The VEGF level was 1799 +/- 478 pg/ml in eyes with DR and not detectable in MH. The PEDF level in proliferative DR (PDR) (0.94 +/- 0.12 microg/ml) was lower than that in nonproliferative DR (NPDR) (2.25 +/- 0.32 microg/ml), and that in active DR (0.85 +/- 0.14 microg/ml) was significantly lower than that in inactive DR (1.59 +/- 0.24 microg/ml; P =.01). The VEGF level was 2025 +/- 533 pg/ml in PDR and 215 +/- 201 pg/ml in NPDR and that in active DR (2543 +/- 673 pg/ml) was significantly higher than that in inactive DR (395 +/- 188 pg/ml; P =.0098). CONCLUSIONS: These results suggest that lower levels of PEDF and higher levels of VEGF may be related to the angiogenesis in DR that leads to active PDR.     

新生血管性青光眼血管内皮生长因子和血小板衍生生长因子含量及其相关影响因素

目的 观察新生血管性青光眼（NVG）患者眼内血管内皮生长因子（VEGF）和血小板衍生生长因子（PDGF）含量,并分析其相关影响因素.方法 实验研究.NVG患者54 例（54眼）,其中视网膜中央静脉阻塞（CRVO）17眼,糖尿病性视网膜病变（DR）22眼,视网膜血管炎（Eales病）4眼,视网膜脱离（RD）术后4眼,未知原因7眼.虹膜新生血管Ⅰ级17眼,Ⅱ级12眼,Ⅲ级13眼,Ⅳ级12眼.36眼曾行视网膜光凝和（或）冷凝治疗.10只新鲜健康角膜供体眼作为正常对照组.抽取两组的房水和玻璃体液样本,采用酶联免疫吸附试验（ELISA）检测其中VEGF和PDGF含量.对NVG组和正常对照组VEGF和PDGF含量的比较采用Mann-Whitney U检验,不同原发病、不同等级虹膜新生血管、视网膜光凝和（或）冷凝治疗组与未治疗组之间VEGF和PDGF含量的比较分别采用方差分析、LsD-t检验和独立样本t检验,并对各组VEGF和PDGF含量进行Pearson相关分析.结果 NVG组房水中VEGF和PDGF含量分别为（926.3±223.5）ng/L和（226.2±81.5）ng/L,玻璃体液中分别为（1096.1±235.9）ng/L和（375.3±141.5）ng/L,均高于正常对照组（Z 房水VECG=-4.993,Z房水PDGF=-4.891,Z玻璃体VEGF=-4.991,Z玻璃体PDGF＝-4.992,P均=0.000）.不同原发病组比较：CRVO组房水和玻璃体液中VEGF含量均高于不明原凶组（t房水=1.746,P房水＝0.033;t玻璃体=1.917,P玻璃体=0.027）,其他各组之间VEGF含量差异均无统计学意义;DR组房水和玻璃体液中PDGF含量高于Eales病组（t房水=1.697,P房水：0.043;t玻璃体=1.762,P玻璃体=0.038）,其他各组间PDGF含量差异均无统计学意义.不同虹膜新牛血管分级组比较：各组房水和玻璃体液中VEGF含量差异均无统计学意义：虹膜新生血管Ⅳ级组玻璃体液中PDGF含量高于Ⅲ级组（t=1.740,P=0.049）.视网膜光凝和（或）冷凝治疗后,房水及玻璃体液中VEGF和PDGF的含量均低于未治疗组（Z房水VEGF＝2.945,P房水VEGF=0.003;t房水PDGF＝3.199,P房水PDGF＝0.002;Z玻璃体VEGF=3.165,P玻璃体VEGF＝002;t玻璃体PDGF＝2.984,P玻璃体PDGF＝0.004）.相关分析显示：NVG组房水中VEGF和PDGF含量呈正相关（r=0.305,P=0.025）,玻璃体液中VEGF和PDGF含量也呈正相关（r=0.303,P＝0.026）;CRVO组玻璃体液中VEGF和PDGF含量呈正相关（r=0.503,P＝0.040）;DR组房水中VEGF和PDGF含量呈正相关（r=0.462,P=0.030）.结论 NVG中VEGF和PDGF含量的变化与其原发病、虹膜新生血管严重程度有关,视网膜光凝和（或）冷凝治疗可抑制VEGF和PDGF的产生.     

抗VEGF辅助PPV治疗增生性糖尿病视网膜病变的效果及作用机制分析

目的:探讨抗血管内皮生长因子(vascular endothelial growth factor,VEGF)辅助玻璃体切割术(pars plana vitrectomy,PPV)治疗增生性糖尿病视网膜病变(proliferative diabetic retinopathy,PDR)的效果及作用机制.方法:将92例92眼行PPV的PDR患者,根据术前有无玻璃体腔注射雷珠单抗(intravitreal ranibizumab,IVR)分为单纯PPV组(41例41眼)和联合治疗组(51例51眼),其中联合治疗组于PPV术前5~7 d进行IVR.比较两组手术时间、电凝次数、硅油填充率、术后并发症发生率、术后3 mo患眼BCVA及手术前后不同时间点房水和玻璃体VEGF、色素上皮衍生因子(pigment epithelium-derived factor,PEDF)含量.结果:联合治疗组手术时间短于单纯PPV组,电凝次数少于PPV组,硅油填充、医源性视网膜裂孔及玻璃体再积血的几率均低于单纯PPV组,差异均有统计学意义(P<0.05);联合治疗组PPV时房水及玻璃体VEGF、PEDF含量低于单纯PPV组,差异均有统计学意义(P<0.05);联合治疗组术后3 mo患眼BCVA好于单纯PPV组,差异有统计学意义(P<0.05).结论:IVR联合PPV治疗PDR可降低PPV围手术期VEGF、PEDF水平,减少术中电凝次数,降低术后医源性视网膜裂孔及玻璃体再积血发生率,提高视力水平.     

Proliferative and inflammatory factors in the vitreous of patients with proliferative diabetic retinopathy

Purpose:

The purpose was to measure the concentrations of various cytokines and growth factors (including vascular endothelial growth factor [VEGF] and pigment epithelium-derived factor [PEDF]) in the vitreous of patients with proliferative diabetic retinopathy (PDR) and to investigate interaction between inflammatory and proliferative factors in the genesis of PDR.

Materials and Methods:

Vitreous samples from 32 eyes with PDR and 25 eyes without diabetes mellitus and signs of DR (control) were collected. Vitreous concentrations of VEGF, PEDF, monocyte chemotactic protein-1 (MCP-1), interleukin-4 (IL-4), IL-6, IL-8, IL-10, IL-17A, and secretory immunoglobulin A (sIgA) were simultaneously measured using enzyme-linked immunoassay.

Results:

Vitreous levels of VEGF, PEDF, IL-17A, IL-6, IL-8, IL-4, and sIgA were significantly (Π < 0.05) higher in eyes with PDR compared to control. The concentration of VEGF was more than 17-times higher than in control, and the concentration of PEDF was not changed oppositely and was also higher (1.45-times) compared to control, that may indicate disturbances of compensatory mechanisms in angiogenesis regulation in PDR. Significant (P < 0.05) positive correlations were observed between vitreous concentrations of VEGF and IL-17A (r = 0.45), VEGF and IL-8 (r = 0.48), VEGF and IL-4 (r = 0.51), PEDF and IL-17A (r = 0.48), PEDF and IL-8 (r = 0.59), MCP-1 and PEDF (r = 0.72), MCP-1 and IL-8 (r = 0.45), IL-4 and IL-17A (r = 0.65), IL-4 and IL-8 (r = 0.71), IL-8 and IL-17A (r = 0.59).

Conclusions:

Significantly raised levels of inflammatory and proliferative factors and numerous positive correlations between them may demonstrate a significant role of activation of vascular proliferation and local inflammation in the pathogenesis of PDR.     

增生性玻璃体视网膜疾病眼内液血管内皮生长因子的表达

目的 观察增生性玻璃体视网膜疾病患者眼内液（房水、玻璃体）中血管内皮生长因子（VEGF）含量的变化规律，探讨VEGF在增生性玻璃体视网膜疾病发展变化中的作用。 方法 采用双抗体夹心酶联免疫吸附试验(ELISA)定量检测增生性玻璃体视网膜病变（PVR）、视网膜静脉阻塞（RVO）、增生性糖尿病视网膜病变（PDR）、新生血管性青光眼（NVG）患者组及正常对照组房水、玻璃体VEGF含量。 结果 PVR、RVO、PDR、NVG患者组房水及玻璃体VEGF含量均高于正常对照组，其差异均有统计学意义(P<0.05)；NVG、PDR、RVO、PVR患者组房水及玻璃体VEGF含量依次降低 ，其差异有统计学意义(P<0.05)；PVR、RVO、PDR、NVG患者组和正常对照组玻璃体VEGF含量均高于房水VEGF含量，其差异有统计学意义(P<0.05)；PVR患者病史与房水、玻璃体VEGF含量呈负相关（r分别为－0.819、－0.823，P＜0.05）；RVO患者病史与房水、玻璃体VEGF含量呈正相关（r分别为0.913、0.929，P＜0.05）；PDR患者玻璃体积血时间与房水、玻璃体VEGF含量呈正相关（r分别为0.905、0.920，P＜0.05）。 结论 增生性玻璃体视网膜疾病患者房水及玻璃体VEGF含量明显增高，VEGF可能在增生性玻璃体视网膜疾病发展变化中起着重要的作用。 (中华眼底病杂志， 2006， 22：313-316）     

Expression of Pigment Epithelium-Derived Factor and Vascular Endothelial Growth Factor in Fibrovascular Membranes from Patients with Proliferative Diabetic Retinopathy

Purpose

The expression of pigment epithelium-derived factor (PEDF), a strong inhibitor of angiogenesis, has not been examined in human ocular fibrovascular membranes, to the best of our knowledge. The purpose of this study was to determine whether PEDF is expressed in the fibrovascular membranes in eyes of patients with proliferative diabetic retinopathy (PDR), and to compare the expression of PEDF with that of vascular endothelial growth factor (VEGF).

Methods

The expression of PEDF and VEGF in the fibrovascular membranes excised during vitreous surgery in eight cases of PDR was determined by immunohistochemistry.

Results

VEGF was strongly expressed in the endothelial cells of newly formed vessels in the fibrovascular membranes. In contrast, PEDF was weakly expressed in the endothelial cells and was prominently expressed in the extracellular matrix and fibrous tissue surrounding the new vessels.

Conclusions

Our results suggest that PEDF, along with VEGF, may modulate the formation of fibrovascular membranes in patients with PDR.?Jpn J Ophthalmol 2006;50:116–120 © Japanese Ophthalmological Society 2006     

Cytokines in the vitreous fluid of patients with proliferative diabetic retinopathy--vascular endothelial growth factor and platelet-derived growth factor are elevated in proliferative diabetic retinopathy]

PURPOSE: To determine the relation between vascular endothelial growth factor (VEGF) and platlet-derived growth factor (PDGF) in the vitreous fluids from patients with proliferative diabetic retinopathy (PDR). SUBJECTS AND METHOD: Concentrations of VEGF and PDGF in the vitreous fluids from 53 eyes, 31 eyes in 30 PDR patients and 22 eyes in 22 non diabetes mellitus(DM) patients serving as controls, were measured by enzyme-linked immunosolvent assay. The levels of VEGF and PDGF were compared between PDR and non DM patients. The relationship between these factors and clinical characteristics such as age, sex, protein concentration in the aqueous humor, HbA1c and duration of diabetes were investigated. RESULTS: Levels of both VEGF and PDGF in the PDR group were significantly higher than in non DM group (p < 0.01). A positive correlation was observed between the levels of VEGF and protein concentration in the aqueous humor (p < 0.01). However, levels of both VEGF and PDGF did not correlate with age, sex, or HbA1c. CONCLUSION: Both VEGF and PDGF were shown to be correlated with the pathogenesis of PDR.     

Proinflammatory cytokines and angiogenic and anti-angiogenic factors in vitreous of patients with proliferative diabetic retinopathy and eales' disease

PURPOSE: To investigate the mechanism of angiogenesis in proliferative diabetic retinopathy (PDR) and Eales' disease (ED) on the basis of the levels of proinflammatory cytokines, angiogenic growth factor, and antiangiogenic factor in the vitreous humor. METHODS: Twenty-five patients with PDR, 10 patients with ED, and 25 with macular hole (MH) as control subjects were studied. The concentration of the proinflammatory cytokines interleukin-6 (IL-6), IL-8, IL-1 beta; chemokine-monocyte chemoattractant protein-1 (MCP-1); angiogenic factor-vascular endothelial growth factor (VEGF); and antiangiogenic factor-pigment epithelium derived factor (PEDF) in the vitreous fluid obtained from the eyes during vitrectomy were measured by sandwich enzyme linked immunosorbent assay (ELISA). RESULTS: IL-6, IL-8, MCP-1, and VEGF levels in the vitreous were significantly higher in PDR (P < 0.0001) and ED (P < 0.0001) than in MH patients. Conversely, the vitreous level of PEDF was significantly reduced in PDR (P < 0.0001) but not in ED. A significant correlation was observed between VEGF and IL-6 in ED patients. CONCLUSION: The authors demonstrate the importance of VEGF in retinal neovascularization of ED which is an idiopathic inflammatory venous occlusion. Further study is required to understand the interrelationship between VEGF and inflammatory cytokines in PDR and ED.     

Increased vitreous levels of hydroimidazolone in type 2 diabetes patients are associated with retinopathy: a case-control study

PURPOSE: As advanced glycation endproducts (AGEs) and the vitreous body are both considered to be involved in the development of diabetic retinopathy and hydroimidazolone is one of the most prominent AGEs, we compared vitreous and serum hydroimidazolone in diabetes patients with proliferative diabetic retinopathy (PDR) to levels in non-diabetes controls, co-measuring vitreous albumin and vascular endothelial growth factor (VEGF). METHODS: In a cross-sectional case-control study design, we used immunoassays to compare vitreous and serum hydroimidazolone and VEGF levels in 23 consecutive type 2 diabetes mellitus patients with a median known diabetes duration of 12 years (range 1-38 years) with those in 32 non-diabetes age-matched controls undergoing vitrectomy. RESULTS: Vitreous hydroimidazolone was increased in the PDR group (median 1.3 U/ml, range 0.5-3.3 U/ml) compared with controls (median 0.8 U/ml, 0.5-2.5 U/ml) (p = 0.026). Hydroimidazolone levels in serum and vitreous correlated (r = 0.49, p = 0.019). In PDR, vitreous VEGF levels were increased (median 1600 pg/ml, range 20-14 700 pg/ml) compared with controls (median 7 pg/ml, range 2-500 pg/ml) (p < 0.001). Similarly, vitreous albumin concentration was increased in PDR (median 1.6 g/l, range 0.7-3.0 g/l) compared with controls (median 0.3 g/l, range 0.08-1.9 g/l) (p < 0.001). Albumin could not explain the differences in vitreous VEGF levels in a logistic regression analysis. No correlation was found between vitreous levels of VEGF and hydroimidazolone (r = 0.12, p = 0.59). CONCLUSIONS: Increased vitreous hydroimidazolone is associated with diabetic retinopathy, possibly due to a blood-retinal barrier breakdown. Irrespective of origin, it may add to the ocular damage and needs further causal investigation. Increased VEGF in diabetic vitreous is probably of intraocular origin. It is not associated with vitreous hydroimidazolone.     

Angiotensin II and vascular endothelial growth factor in the vitreous fluid of patients with proliferative diabetic retinopathy

AIMS: To investigate the correlation between the level of angiotensin II and vascular endothelial growth factor (VEGF) in the vitreous fluid and the severity of proliferative diabetic retinopathy (PDR). METHODS: During vitreoretinal surgery at the Tokyo Women's Medical University, vitreous fluid samples were obtained from 51 eyes of diabetic patients with PDR, six eyes of diabetic patients without retinopathy, and 16 eyes of non-diabetic patients with ocular disease (controls). The VEGF levels in vitreous fluid and plasma were determined by enzyme linked immunosorbent assay, while angiotensin II levels were measured by radioimmunoassay. RESULTS: The vitreous fluid levels of VEGF and angiotensin II were significantly higher in patients with PDR than in non-diabetic patients or diabetic patients without retinopathy (all p<0.0001). The vitreous fluid level of angiotensin II was significantly correlated with that of VEGF (p<0.0001), and the vitreous concentrations of both VEGF and angiotensin II were significantly higher in patients with active PDR than in those with quiescent PDR (p<0.0001 and p=0.0005, respectively). CONCLUSION: The authors found that both angiotensin II and VEGF levels were significantly higher in the vitreous fluid of patients with PDR than in that of non-diabetic patients or diabetic patients without retinopathy, and that the levels of both angiotensin II and VEGF were elevated in the active stage of PDR. These findings suggest that angiotensin II contributes to the development and progression of PDR in combination with VEGF.     

增生型糖尿病视网膜病变眼内液中血管内皮生长因子定量测定

目的：检测增生型糖尿病视网膜病变（PDR）患者房水和玻璃体中血管内皮生长因子（VEGF）水平。方法：应用酶联免疫吸附测定法（ELISA）。结果：房水VEGF含量,PDR患者（4例）较正常人升高,差异有显著性（P＜0.05）。玻璃体VEGF的含量,PDR患者（11例）较正常人（10例）升高,差异有显著性（P＜0.05）。结论：PDR患者房水和玻璃体中VEGF的含量升高,在PDR的病理过程中起一定的作用。     

Positive association of pigment epithelium-derived factor with total antioxidant capacity in the vitreous fluid of patients with proliferative diabetic retinopathy

BACKGROUND: Pigment epithelium-derived factor (PEDF), a glycoprotein with potent neuronal differentiating activity, was recently found to inhibit advanced glycation end product (AGE)-induced retinal hyperpermeability and angiogenesis through its antioxidative properties, suggesting that it may exert beneficial effects on diabetic retinopathy by acting as an endogenous antioxidant. However, the inter-relationship between PEDF and total antioxidant capacity in the eye remains to be elucidated. AIMS: To determine vitreous PEDF and total antioxidant levels in patients with proliferative diabetic retinopathy (PDR), and to investigate the relationship between them. METHODS: Vitreous levels of PEDF and total antioxidant capacity were measured by an ELISA in 39 eyes of 36 patients with diabetes and PDR and in 29 eyes of 29 controls without diabetes. RESULTS: Vitreous levels of total antioxidant capacity were significantly lower in patients with diabetes and PDR than in controls (mean (SD) 0.16 (0.05) vs 0.24 (0.09) mmol/l, respectively, p<0.001). PEDF levels correlated positively with total antioxidant status in the vitreous of patients with PDR (r = 0.37, p<0.05) and in controls (r = 0.41, p<0.05). Further, vitreous levels of PEDF in patients with PDR without vitreous haemorrhage (VH(-)) were significantly (p<0.05) decreased, compared with those in the controls or in patients with PDR with vitreous haemorrhage (VH(+); PDR VH(-), 4.5 (1.1) microg/ml; control, 7.4 (4.1) microg/ml; PDR VH(+) 8.5 (3.6) microg/ml). CONCLUSION: This study demonstrates that PEDF levels are associated with total antioxidant capacity of vitreous fluid in humans, and suggests that PEDF may act as an endogenous antioxidant in the eye and could play a protective role against PDR.     

增生性糖尿病视网膜病变患者玻璃体内血管内皮生长因子的表达

目的 探讨增生性糖尿病视网膜病变(PDR)患者玻璃体内血管内皮生长因子(VEGF)的表达及相关影响因素.方法 病例对照研究.对50例(50只眼)接受玻璃体切除治疗的PDR患者进行分析.术中获取玻璃体标本,并用双抗体夹心酶联免疫吸附试验ELISA法对术中获取的玻璃体标本进行VEGF含量的定量检测,并分析增生性糖尿病视网膜病变患者玻璃体内VEGF的表达情况.平均随访9个月(6～26个月).用成组t检验比较PDR组和正常对照组玻璃体VEGF含量差异,以及硅油填充组与非硅油填充组VEGF含量差异.用方差分析方法比较PDR进展组、稳定组和好转组玻璃体VEGF含量有无差异.用单因素方差分析方法分析玻璃体VEGF含量对PDR术后疗效的影响.结果 PDR组玻璃体VEGF含量平均(592.4801±587.4267)ng/L,正常对照组玻璃体VEGF含量平均(131.3022±26.9192)ng/L.PDR组玻璃体VEGF含量高于对照组(t=3.2315,P＜0.05).术后PDR进展有10只眼(20%),稳定10只眼(20%),好转30只眼(60%).PDR进展组玻璃体VEGF含量显著高于PDR稳定和好转组(q=-3.3187,-4.0843;P＜0.05).术前未接受视网膜光凝组玻璃体VEGF含量显著高于接受全视网膜光凝或局部视网膜光凝组(q=-4.2187,-3.9672;P＜0.05).结论玻璃体VEGF表达与PDR严重程度有一定关系.术后PDR稳定或好转者玻璃体VEGF水平呈相对低表达.(中华眼科杂志,2009,45:206-209)     

Soluble IL-6 Receptor in Vitreous Fluid of Patients with Proliferative Diabetic Retinopathy

Purpose

To identify the biological reaction of soluble interleukin-6 receptor (sIL-6R) in the vitreous of patients with proliferative diabetic retinopathy (PDR).

Methods

The subjects were 45 patients (45 eyes) with vitreoretinal diseases. The patients were divided into three groups: the PDR group comprised 28 patients (28 eyes) with PDR; the pre-proliferative diabetic retinopathy (PPDR) group comprised seven patients (seven eyes) with PPDR combined with diabetic macular edema; and the nondiabetic group comprised ten patients (ten eyes) with idiopathic macular hole or idiopathic epiretinal membrane. Vitreous samples were obtained at vitrectomy. sIL-6R, vascular endothelial growth factor (VEGF), and protein concentration in vitreous samples were determined by enzyme-linked immunosorbent assay (ELISA). sIL-6R levels in serum were also determined by ELISA in nine of the 28 patients with PDR and in six healthy volunteers as controls.

Results

In vitreous fluid, the levels of sIL-6R in the PDR group, PPDR group, and nondiabetic group were 612.7 ± 233.8 (mean ± SD), 746.3 ± 523.1, and 215.4 ± 98.3?pg/ml, respectively. Vitreous levels of sIL-6R in the PDR and PPDR groups were significantly higher than those in the nondiabetic group (PDR group, P < 0.0001; PPDR group, P < 0.01). In serum, the levels of sIL-6R were 39.38 ± 9.43?ng/ml in the PDR group and 22.84 ± 5.32?ng/ml in the control group. sIL-6R levels in serum in the PDR group were significantly higher than those in the control group (P < 0.01). A partial correlation analysis showed a significant correlation between the levels of sL-6R and VEGF in the vitreous in the PDR group (r = 0.34, P < 0.05).

Conclusions

We conclude that the level of sIL-6R in vitreous fluid can be considered as a biomarker of PDR.?Jpn J Ophthalmol 2007;51:100–104 © Japanese Ophthalmological Society 2007