Angiopoietin concentrations in diabetic retinopathy

BACKGROUND/AIM: Angiopoietin 1 and 2 interact with vascular endothelial growth factor (VEGF) to promote angiogenesis in animal and in vitro models. Although VEGF concentrations are elevated, there is little information regarding angiopoietin concentration in the vitreous of patients with diabetic retinopathy. METHODS: Angiopoietin concentrations were measured by luminescence immunoassay in vitreous samples from 17 patients with non-proliferative diabetic retinopathy (NPDR) and clinically significant diabetic macular oedema (CSMO), 10 patients with proliferative diabetic retinopathy (PDR), and five patients with macular hole (controls) obtained at pars plana vitrectomy. RESULTS: Angiopoietin 1 concentrations were low in patients with macular hole (median 17 pg/ml) while in NPDR with CSMO they were 2002 pg/ml (range 289-5820 pg/ml) and in PDR 186 pg/ml (range 26-2292 pg/ml). Angiopoietin 2 concentrations in NPDR with CSMO were a median of 4000 pg/ml (range 1341-14 329 pg/ml). For both macular hole and PDR patients angiopoietin 2 was below the limit of detection. CONCLUSIONS: Angiopoietin 2 concentration was twice that of angiopoietin 1 in NPDR with CSMO. Angiopoietin 2 is the natural antagonist of angiopoietin 1 which is thought to act as an anti-permeability agent. The predominance of angiopoietin 2 may allow VEGF induced retinal vascular permeability in patients with CSMO. The relatively low concentration of both angiopoietin 1 and 2 in patients with proliferative diabetic retinopathy may reflect the established nature of the neovascularisation in cases proceeding to vitrectomy.     

Vitreous levels of angiopoietin 2 and vascular endothelial growth factor in patients with proliferative diabetic retinopathy

PURPOSE: To investigate the levels of angiopoietin-2 (Ang2) and vascular endothelial growth factor (VEGF) in the vitreous fluids of patients with proliferative diabetic retinopathy (PDR) and to ascertain their involvement, if any, in angiogenesis of PDR. DESIGN: Retrospective case-control study. METHODS: Forty-one eyes of 41 patients with proliferative diabetic retinopathy and 18 eyes of 18 patients with nondiabetic ocular diseases (control group). Nondiabetic control eyes included 11 with idiopathic macular hole and 7 with idiopathic epiretinal membrane. Vitreous fluid samples were obtained at vitrectomy, and the levels of Ang2 and VEGF were measured by enzyme-linked immunosorbent assay. RESULTS: Vitreous level (mean +/- SD) of Ang2 was significantly higher in patients with PDR (1,753 +/- 3,213 pg/ml) than in control patients (112 +/- 113 pg/ml) (P < .0001). The vitreous concentration of VEGF was also significantly higher in patients with PDR (812 +/- 1,108 pg/ml) than in control patients (1.7 +/- 4.4 pg/ml) (P < .0001). Both Ang2 and VEGF levels in eyes with active PDR were significantly higher than in those with inactive PDR. The vitreous concentration of Ang2 correlated significantly with that of VEGF in eyes with proliferative diabetic retinopathy ([correlation coefficient] rho = 0.497, P = .001). CONCLUSIONS: These data demonstrate an increase of Ang2 in the vitreous fluid of patients with PDR and suggest an association of Ang2 and VEGF with angiogenic activity in PDR.     

增殖性糖尿病视网膜病变玻璃体SDF-1和VEGF的含量分析

研究增殖性糖尿病视网膜病变患者玻璃体基质细胞衍生因子（Stromalcell—derivedfactor-1。SDF-1）和血管内皮生长因子（Vascularendothelialgrowthfactor，VEGF）的浓度，及其相互作用关系。方法：酶联免疫吸附法（Enzyme-linkedimmunosorbentassay，ELISA）检测玻璃体内SDF-1和VEGF的含量，每个标本重复3次。实验组为增殖性糖尿病视网膜病变（Proliferativediabeticretinopathy，PDR）的住院患者30例，对照组为同期行玻璃体切除术的特发性黄斑裂孔患者12例。结果：PDR患者玻璃体VEGF的平均浓度为（2865．87±387．85）pg／ml，明显高于特发性黄斑裂孔组[（142．42±21．03）pg／ml，P〈0．0001]。增殖性糖尿病视网膜病变患者玻璃体SDF-1的含量平均为（298．40±24．57）pg／ml，对照组为（86．9l±15．89）pg／ml，两组的差异具有统计学意义（P〈0．0001）。在30例PDR患者玻璃体内VEGF和SDF-1的含量表现为正相关（Pearson相关系数r=0．62，P〈0．001）。结论：增殖性糖尿病患者玻璃体SDF-1和VEGF的含量均高于非糖尿病患者，提示SDF-1和VEGF共同参与了增殖性糖尿病视网膜病变患者病理性新生血管的形成过程。     

Vitreous and aqueous concentrations of proangiogenic, antiangiogenic factors and other cytokines in diabetic retinopathy patients with macular edema: Implications for structural differences in macular profiles

The aim of the study was to determine anatomical and growth factor profiles in patients with clinically significant macular oedema (CSMO) undergoing pars plana vitrectomy (PPV). Twenty patients with moderate nonproliferative diabetic retinopathy (NPDR) with persistent CSMO underwent PPV. Patients had baseline and postoperative clinical assessment including Ocular Coherence Tomography (OCT). Baseline vitreous and aqueous and serial postoperative aqueous samples were analysed for vascular endothelial growth factor-A (VEGF-A), pigment epithelium derived Factor (PEDF) and other factors (pg/ml) including hepatocyte growth factor, MMP 9, soluble flt-1 Receptor, and TGF beta1 by ELISA. Vitreous from patients with full thickness macular holes (8) and proliferative diabetic retinopathy (22) were collected for comparison as controls. Vitreous VEGF-A concentration in the NPDR group was 957 pg/ml compared to 239 pg/ml in the macula hole (FTMH) control (p < 0.0001) and 596 pg/ml compared to PDR (p = 0.006). The median diabetic vitreous PEDF concentration was 1.36 microg/ml (FTMH 2.6 microg/ml p = 0.05). In NPDR, it was higher (1.59 microg/ml) than PDR (1.27 microg/ml) p = 0.02. There were changes to the HGF, soluble flt-1 Receptor and TGF b1 concentrations in the NPDR compared to either PDR or the normal state. In CSMO, two OCT profiles were identified: dome-shaped macular elevation (Group 1) (n = 4) and diffuse-low elevation profile (Group 2) (n = 16) which also showed differences in the postoperative median aqueous VEGF concentrations despite macular volume decreasing for both. The results suggest that there is an up-regulation of VEGF in the vitreous of the diabetic eye with a reciprocal decrease in PEDF. The structural and molecular differences between the two OCT macular profiles may explain the varying response to PPV in patients with diffuse CSMO.     

Intravitreous high expression level of netrin-1 in patients with proliferative diabetic retinopathy

 Abstract Purpose: To investigate the significance of netrin-1 and vascular endothelial growth factor (VEGF) in the pathogenesis of retinal angiogenesis, the levels of netrin-1 and VEGF in the vitreous fluid and serum of the proliferative diabetic retinopathy (PDR) and non-proliferative diabetic retinopathy (non-PDR) patients were measured. We then determined the netrin-1 and VEGF expression in the oxygen induced retinopathy (OIR) mice retina. Methods: A total of 18 eyes from 18 patients were included in our study and 10 of them were collected from PDR patients and 8 from non-PDR patients. Undiluted vitreous fluid samples were collected during pars plana vitrectomy. Appropriate blood samples were collected if possible. Netrin-1 and VEGF levels in the vitreous fluid and plasma were determined by Enzyme-linked Immunosorbent Assays. OIR mice models were established, and netrin-1 and VEGF levels were determined by immunohistochemistry analysis.  Results: The levels of netrin-1 and VEGF in the vitreous of PDR patients were significantly higher than those in the controls (Mediannetrin-1=509.94 vs. 85.91 pg/ml, P<0.001 and Median VEGF=762.60 vs. 77.52 pg pg/ml, P<0.001). Netrin-1 was mainly expressed in GCL and INL of the retina in mice. Both netrin-1 and VEGF were up-regulated in OIR mice. Conclusion: Netrin-1 and VEGF levels were elevated in vitreous fluid of the PDR patients and the OIR mice retina. Therefore, netrin-1 may play an important role in pathological retinal angiogenesis.     

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。     

Different plasma levels of vascular endothelial growth factor and nitric oxide between patients with choroidal and retinal neovascularization

Because the blood flow is much more intense in the choroid than in the retina, it is interesting to explore whether choroidal neovascularization (CNV) is more influenced by plasma angiogenic factors than retinal neovascularization. The aim of this study was to investigate plasma profiles of vascular endothelial growth factor (VEGF) and nitric oxide (NO) in patients with CNV due to age-related macular degeneration (AMD) and in those with retinal neovascularization due to proliferative diabetic retinopathy (PDR). Seventy-seven subjects with AMD, 22 with PDR, and 42 nondiabetic, non-AMD controls were enrolled in this comparative case series. AMD subjects were classified into three groups: dry type (dry AMD, n = 17), wet type with active CNV (CNV/AMD, n = 42), and disciform scar due to advanced wet AMD (scar/AMD, n = 18). Plasma VEGF and NO levels of each subject were measured with enzyme-linked immunosorbent assay and chemiluminescence, respectively. Plasma VEGF level in CNV/AMD (median 256.0 pg/ml, interquartile range 146.4-375.3 pg/ml) was significantly higher than in PDR (124.8 pg/ml, 75.7-215.3 pg/ml; p = 0.004) and controls (120.3 pg/ml, 82.8-168.2 pg/ml, p =0.001). CNV/AMD also had the highest VEGF level among the AMD subgroups. Plasma NO level was significantly elevated in PDR (137.4 microM, 63.7-240.1 microM) when compared with CNV/AMD (71.8 microM, 42.4-113.3 microM; p = 0.004) and controls (62.6 microM, 39.0-114.9 microM; p = 0.002). There was no significant difference in NO levels among the AMD subgroups. No significant correlation between VEGF and NO levels was noted. These findings indicate that both circulating VEGF and NO may play different roles in the pathogenesis of retinal neovascularization and CNV.     

Elevated Vascular Endothelial Growth Factor Levels in the Vitreous of Patients With Proliferative Diabetic Retinopath

Objective: To detect the levels of vascular endothelial growth factor (VEGF) in the vitreous of patients with proliferative diabetic retinopathy (PDR) and to investigate the possible role of VEGF in the development of neovascularization in PDR. Methods ; Undiluted vitreous samples and fasting venous blood samples were obtained from 27 patients with PDR and 14 subjects with idiopathic macular hole who underwent pars plana vitrectomy. The concentration of VEGF was determined by quantitative enzyme - linked immunosorbent assay (ELISA).Results: The level of vitreous VEGF in patients with PDR (median 0. 41ng/ml, range 0. 09- 11. 56ng/ml) was significantly elevated when compared with that in control subjects (median 0.017ng/ml, range 0.008-0.04ng/ml)(P<0. 001). The median of PDR patients' serum VEGF concentration was 0.19ng/ml (0. 090. 46ng/ ml) which was far lower than vitreous VEGF concentration (P<0. 05). Vitreous VEGF concentration was higher in PDR patients with retinal detachment than that in patient wi     

Comparison of the levels of hepatocyte growth factor and vascular endothelial growth factor in aqueous fluid and serum with grades of retinopathy in patients with diabetes mellitus.

AIMS: To determine the relation between the stages of diabetic retinopathy (DR) and the levels of hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) in aqueous fluid and serum. METHODS: Levels of HGF and VEGF in serum and aqueous humour obtained during ocular surgery were measured by enzyme linked immunosorbent assay in 58 diabetic patients with 32 non-diabetic patients (NDM) as controls. The patients with diabetes were classified into three groups according to the stage of DR: no DR (NDR; 15 cases), non-proliferative DR (NPDR; six cases), and proliferative DR (PDR; 37 cases). RESULTS: No significant differences were found between any of the groups in serum concentrations of HGF or VEGF. The aqueous HGF levels increased with the stage of DR: NDM, median 397 pg/ml, range 133-930 pg/ml; NDR, 371 pg/ml, 142-1536 pg/ml; NPDR, 455 pg/ml, 162-1007 pg/ml; and PDR, 638 pg/ml, 187-2222 pg/ml. The aqueous VEGF levels in PDR (median 212 pg/ml, range 14-1216 pg/ml) were significantly higher than in NDM (105 pg/ml, 9-203 pg/ml), but aqueous HGF concentrations were unrelated to those of VEGF. CONCLUSION: The results of the present study suggest that both HGF and VEGF present in the ocular tissues may play important roles in the progression of DR.     

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.     

Interleukin-8, nitric oxide and glutathione status in proliferative vitreoretinopathy and proliferative diabetic retinopathy

PURPOSE: To evaluate interleukin-8 (IL-8), nitric oxide (NO) and glutathione (GSH) profiles in vitreous humor and blood samples in patients with proliferative diabetic retinopathy (PDR) and in patients with proliferative vitreoretinopathy (PVR) and to compare the levels with those of controls. PATIENTS AND METHODS: NO concentrations were determined by using the Greiss reaction in plasma and vitreous humor samples. GSH levels were determined in both blood and vitreous humor samples, using DTNB, a disulfide chromogen. Vitreous IL-8 were assayed by ELISA. Twenty-three patients with PDR, 18 patients with PVR and 21 cadavers as the control group were included in the study. RESULTS: Plasma and vitreous NO levels were found to be 25.6 +/- 2.1 and 36.9 +/- 3.0 micromol/l in patients with PDR, 27.0 +/- 4.7 and 34.3 +/- 2.9 micromol/l in patients with PVR and 17.4 +/- 2.7 and 15.9 +/- 1.4 micromol/l in controls, respectively. Vitreous humor and plasma NO levels did not show any statistically significant difference between PDR and PVR groups. However, the values for vitreous in both groups were significantly higher than those of controls (p < 0.0001). Although IL-8 levels in vitreous samples of patients with PDR were not significantly different (79.6 +/- 9.7 pg/ml) from those of patients with PVR (42.2 +/- 7.3 pg/ml) (p = 0.06), the levels in both groups were significantly higher than those of controls (19.0 +/- 3.9 pg/ml) (p < 0.0001 and p < 0.05, respectively). Blood and vitreous GSH levels were found to be 5.3 +/- 0.4 micromol/g. Hb and 0.58 +/- 0.16 micromol/l in patients with PDR and 8.4 +/- 0.5 micromol/g. Hb and 15.7 +/- 2.2 micromol/l in patients with PVR and 12.0 +/- 1.1 micromol/g. Hb and 0.26 +/- 0.03 mmol/l in controls, respectively. Vitreous and blood GSH levels were significantly lower in patients with PDR compared to those with PVR (p < 0.0001 for both). CONCLUSION: Elevated levels of vitreous and plasma NO and vitreous IL-8 in PDR and PVR implicate a role for these parameters in the proliferation in these ocular disorders. GSH concentrations both in vitreous and blood samples of the PVR and PDR patients were much less than those observed in the control group. Lower GSH concentrations detected in PDR in comparison with those in PVR in vitreous humor and to a lesser degree in blood may play an important role in pathogenesis of new retinal vessel formation in patients with PDR. This also suggests that oxidative stress may be involved in the pathogenesis of PVR and particularly that of PDR.     

增殖性糖尿病视网膜病变患者玻璃体中血管内皮细胞生长因子含量…

检测增殖性糖尿病视网膜病变患者玻璃体中血管内皮细胞生长因子的含量并与正常人进行对比研究，探讨了ＶＥＧＦ在ＰＤＲ病理过程中的作用。应用酶联免疫吸附测定法对７例正常人及１９例ＰＤＲ患者玻璃体中的ＶＥＧＦ进行定量分析研究。结果７例正常人玻璃体中，ＶＥＧＦ的含量为０．１８－０．６０ｎｇ／ｍｌ，平均值为０．３５ｎｇ／ｍｌ。     

糖尿病视网膜病变患者房水VEGF和IL-6水平的测定及其临床意义

目的 探讨糖尿病视网膜病变(DR)程度与房水中血管内皮生长因子(VEGF)和白细胞介素-6(IL-6)含量之间的关系.方法 采用双抗体夹心酶联免疫吸附(EIISA)法,测定88例房水中VEGF和IL-6的含量,根据散瞳眼底检查和眼底荧光素血管造影检查后,实验组分为:无糖尿病视网膜病变组(NDR)21例、单纯型糖尿病性视...     

Macrophage migration inhibitory factor levels in the vitreous of patients with proliferative diabetic retinopathy

AIMS: To assess the potential role of macrophage migration inhibitory factor (MIF) in the pathogenesis of proliferative diabetic retinopathy (PDR). METHODS: MIF levels were assayed in the vitreous and paired serum samples of 73 consecutive patients with PDR (32 eyes) and macular hole or idiopathic epiretinal membrane (controls, 41 eyes). An enzyme linked immunosorbent assay technique was used to determine the concentrations of MIF. RESULTS: The median vitreous level of MIF was 11.93 ng/ml (range 4.16-103.85) in the patients with PDR, and 1.79 ng/ml (undetectable-8.93) in the controls. Vitreous levels in eyes with PDR were significantly greater than those in the controls (p<0.0001). Vitreous levels were significantly higher than serum levels in eyes with PDR (p=0.0026). MIF levels were significantly higher in the vitreous of PDR patients with severe fibrous proliferation than in those with slight proliferation (p<0.05). CONCLUSION: The results indicate increased levels of MIF in the vitreous of patients with PDR and a significant association between MIF levels and grades of fibrous proliferation, suggesting the possibility that MIF may play a part in the development of the proliferative phase of PDR.     

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.     

VEGF、IL-6的水平与糖尿病视网膜病变关系的研究

目的:检测2型糖尿病患者眼房水中血管内皮生长因子(Vascular endothelial growth factor,VEGF)和白细胞介素-6(Interleukin-6,IL-6)的含量,并探讨其临床意义.方法:在白内障手术过程中获取66例2型糖尿病患者的房水,采用双抗体夹心酶联免疫吸附(ELISA)法测定VEGF和IL-6的含量.根据手术后散瞳眼底检查和眼底荧光素血管造影检查确定糖尿病视网膜病变的分期.实验组分为:无糖尿病视网膜病变组(NDR)21例、单纯型糖尿病性视网膜病变组(BDR)26例、增生型糖尿病性视网膜病变组(PDR)19例,正常对照组为健康的老年性白内障患者20例.结果:NDR组、BDR组、PDR组的房水VEGF含量分别为(240.30±26.15)pg/ml、(292.27±58.91)pg/ml、(477.41±91.01)pg/ml,IL-6含量分别为(160.83±33.41)pg/ml、(238.60±62.23)pg/ml、(389.13±90.35)pg/ml,对照组房水VEGF含量为(140.58±26.27)pg/ml、IL-6含量为(82.72±21.53)pg/ml,对照组与实验组比较差异均有统计学意义(F=113.67,P＜0.01;F=106.53,P＜0.01).实验组房水中的VEGF与IL-6含量有相关性(r=0.995,P＜0.01);糖尿病患者的病程与房水中VEGF(r=0.792,0.826,0.841均P＜0.01)、IL-6(r=0.829,0.817,0.896均P＜0.01)含量有相关性.结论:VEGF、IL-6在糖尿病视网膜病变的形成过程中有重要作用,且两者之间有相关性.     

Hepatocyte growth factor in vitreous and serum from patients with proliferative diabetic retinopathy

BACKGROUND: Hepatocyte growth factor (HGF) is an endothelium specific growth factor that has been implicated in angiogenesis, a crucial event for the development of proliferative diabetic retinopathy (PDR). The aim of the study is to determine the intravitreous concentrations of HGF in diabetic patients with PDR, and to investigate whether its serum levels could contribute to its intravitreous concentration. METHODS: 17 diabetic patients and seven non-diabetic patients in whom a vitrectomy was performed were studied. Both groups were matched by serum levels of HGF. Venous blood and vitreous samples were collected simultaneously at the time of vitreoretinal surgery. Vitreous and serum HGF were determined by ELISA. RESULTS: Intravitreous concentrations of HGF (median and range) were higher in diabetic patients (17.04 ng/ml (9.98-80)) in comparison with non-diabetic patients (5.88 ng/ml (2.57-14.20); p=0. 003). Intravitreous HGF concentrations were strikingly higher than serum HGF concentrations both in diabetic patients (17.04 ng/ml (9. 98-80) v 0.66 ng/ml (0.26-1.26); p<0.001) and in the control group (5.88 ng/ml (2.57-14.20) v 0.68 ng/ml (0.49-0.96); p=0.003). No correlation was found between serum and vitreous levels of HGF in both groups (diabetic patients, r= -0.31; p=0.5 and control subjects r= -0.15; p=0.5). CONCLUSION: The high vitreous levels of HGF observed in diabetic patients with PDR cannot be attributed to serum diffusion across the blood-retinal barrier. Therefore, intraocular synthesis appears to be the main contributing factor for the high vitreous HGF concentrations in diabetic patients, a cytokine that seems to be directly involved in the pathogenesis of PDR.     

Correlation between angiotensin-converting enzyme, vascular endothelial growth factor, and matrix metalloproteinase-9 in the vitreous of eyes with diabetic retinopathy

PURPOSE: To investigate the involvement of angiotensin-converting enzyme (ACE) with angiogenic factors, vascular endothelial growth factor (VEGF), and matrix metalloproteinase (MMP)-9 in the vitreous of eyes with proliferative diabetic retinopathy (PDR). DESIGN: Observational case series. METHODS: Angiotensin-converting enzyme activity in the vitreous was measured by using a synthetic substrate for ACE. VEGF and MMP-9 concentrations were determined by enzyme-linked immunosorbent assay. RESULTS: Vitreous ACE activity was significantly higher in eyes with PDR (1.4 +/- 1.3 mU/ml) than in eyes with macular holes (0.22 +/- 0.11 mU/ml). Vitreous VEGF concentration in the eyes with PDR (1067 +/- 1076 pg/ml) was significantly higher than in eyes with macular holes (34 +/- 5.5 pg/ml). Vitreous MMP-9 concentration was also significantly higher in eyes with PDR (7.5 +/- 3.8 ng/ml) than in eyes with macular holes (4.2 +/- 1.4 ng/ml). Significant correlations between ACE and VEGF (P < .01) and between ACE and MMP-9 (P < .01) were observed in the vitreous of eyes with PDR. CONCLUSIONS: Angiotensin-converting enzyme was significantly correlated with angiogenic factors, VEGF and MMP-9, in the vitreous of eyes with PDR.     

Monocyte chemotactic protein-1 in the vitreous of patients with proliferative diabetic retinopathy.

PURPOSE: To investigate the correlation between monocyte chemotactic protein-1 (MCP-1) levels in the vitreous and clinical findings in eyes with proliferative diabetic retinopathy (PDR). METHODS: We assayed MCP-1 levels by ELISA in vitreous samples of 88 consecutive patients with PDR (52 eyes) and macular holes or idiopathic epimacular membrane (controls, 36 eyes). RESULTS: The level of MCP-1 in the vitreous was 2,097.5 +/- 1,099.4 pg/ml (mean +/- SD) in PDR, and 504.3 +/- 405.6 pg/ml in the controls. In PDR eyes, multivariate regression analysis revealed a significant association between MCP-1 levels in the vitreous and the degree of proliferative membrane, and a significant negative association between MCP-1 levels and the extent of preoperative retinal photocoagulation. CONCLUSION: The results suggest that MCP-1 may play a role in the development of the proliferative phase of PDR.     

Concentration of haemodynamic and inflammatory related cytokines in diabetic retinopathy

AIM: There are changes in blood flow during the clinical stages of diabetic retinopathy with increasing leukostasis and secondary elaboration of cytokines. This study evaluated the vitreous concentrations of haemodynamic-related (endothelin-1 (ET-1) and nitric oxide (NO)), inflammatory and anti-inflammatory (interleukin-1 receptor antagonist, IL-1 Ra) cytokines in the diabetic patients (with nonproliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR)), compared them with those of control patients (full thickness macular hole, FTMH) and correlated to macular structural indices. METHOD: Vitreous samples from five FTMH patients representing normal controls were analysed together with the vitreous samples of 15 patients with NPDR and five with PDR. The vitreous concentrations of nitrite (total NO), ET-1, and prostacyclin was determined using ELISA kits (R&D Systems, Minneapolis, MN, USA) according to the manufacturer's instructions. A sandwich luminescent immunoassay technique was used to determine IL-1beta and IL-1 Ra concentrations. RESULTS: In the different clinical groups, there were no differences in the vitreous NO and prostacyclin concentrations. In NPDR, the median ET-1 concentration (0.7 pg/ml SD +/-0.8 pg/ml) was significantly reduced (P<0.05), compared to PDR (6.35 pg/ml SD +/-0.6 pg/ml) and FTMH (3.6 pg/ml SD +/-0.14 pg/ml). Its concentration also positively correlated with foveal thickness and macular volume (P<0.05) in patients with NPDR and macular oedema. IL-1 beta was detected in PDR, and diabetic patients demonstrated a lower concentration of the anti-inflammatory cytokine IL-1 Ra. CONCLUSION: Reduced concentrations of ET-1 in NPDR may reflect the haemodynamic changes of NPDR. The IL-1 Ra concentration suggests a change in the anti-inflammatory environment of the diabetic retina.