scholarly journals High-Mobility Group Box-1 and Endothelial Cell Angiogenic Markers in the Vitreous from Patients with Proliferative Diabetic Retinopathy

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Ahmed M. Abu El-Asrar ◽  
Mohd Imtiaz Nawaz ◽  
Dustan Kangave ◽  
Marwan Abouammoh ◽  
Ghulam Mohammad

The aim of this study was to measure the levels of high-mobility group box-1 (HMGB1) in the vitreous fluid from patients with proliferative diabetic retinopathy (PDR) and to correlate its levels with clinical disease activity and the levels of vascular endothelial growth factor (VEGF), the angiogenic cytokine granulocyte-colony-stimulating factor (G-CSF), the endothelial cell angiogenic markers soluble vascular endothelial-cadherin (sVE-cadherin), and soluble endoglin (sEng). Vitreous samples from 36 PDR and 21 nondiabetic patients were studied by enzyme-linked immunosorbent assay. HMGB1, VEGF, sVE-cadherin, and sEng levels were significantly higher in PDR patients than in nondiabetics (P=0.008; <0.001; <0.001; 0.003, resp.). G-CSF was detected in only 3 PDR samples. In the whole study group, there was significant positive correlation between the levels of HMGB1, and sVE-cadherin (r=0.378,P=0.007). In PDR patients, there was significant negative correlation between the levels of sVE-cadherin and sEng (r=−0.517,P=0.0005). Exploratory regression analysis identified significant associations between active PDR and high levels of VEGF (odds ratio = 76.4; 95% confidence interval = 6.32–923) and high levels of sEng (odds ratio = 6.01; 95% confidence interval = 1.25–29.0). Our findings suggest that HMGB1, VEGF, sVE-cadherin and sEng regulate the angiogenesis in PDR.

2020 ◽  
Vol 17 (4) ◽  
pp. 147916412094098
Author(s):  
Zhong Lin ◽  
Dong Li ◽  
Gang Zhai ◽  
Yu Wang ◽  
Liang Wen ◽  
...  

Purpose: To investigate the association between high myopia and diabetic retinopathy, and its possible mechanism, in a northeastern Chinese population with type 2 diabetic mellitus. Methods: Patients were included from Fushun Diabetic Retinopathy Cohort Study. High myopia was defined as spherical equivalent of autorefraction less than −5D. Results: A total of 1817 patients [688 (37.9%) diabetic retinopathy, 102 (5.6%) high myopia] were included. Compared to eyes without high myopia, the frequency of diabetic retinopathy and non-proliferative diabetic retinopathy was significantly less in eyes with high myopia (23.5% vs 38.7%, p = 0.002; 22.5% vs 35.3%, p = 0.005). Eyes with high myopia were less likely to have diabetic retinopathy (multivariate odds ratio, 95% confidence interval: 0.39, 0.22–0.68) or non-proliferative diabetic retinopathy (odds ratio, 95% confidence interval: 0.40, 0.23–0.70). High myopia was negatively associated with central retinal venular equivalent (multivariate β, 95% confidence interval: −37.1, −42.3 to −31.8, p < 0.001). Furthermore, central retinal venular equivalent (per 10 μm increase) had a significant association with diabetic retinopathy (odds ratio, 95% confidence interval: 1.24, 1.17–1.31) as well as non-proliferative diabetic retinopathy (odds ratio, 95% confidence interval: 1.24, 1.18–1.31). Conclusions: High myopia was negatively associated with both diabetic retinopathy and non-proliferative diabetic retinopathy in this northeastern Chinese population. This protective effect may have been partially achieved via thinning retinal veins.


2019 ◽  
Vol 16 (6) ◽  
pp. 498-505 ◽  
Author(s):  
Xiao Zhang ◽  
Su Chi Lim ◽  
Subramaniam Tavintharan ◽  
Lee Ying Yeoh ◽  
Chee Fang Sum ◽  
...  

Objective: Arterial stiffness has been associated with diabetic retinopathy; however, the information is limited in Asians. We aim to examine the association of central arterial stiffness with the presence and severity of diabetic retinopathy in type 2 diabetes mellitus patients in Singapore. Methods: Arterial stiffness was estimated by carotid-femoral pulse wave velocity and augmentation index using applanation tonometry method. Digital colour fundus photographs from 1,203 patients were assessed for diabetic retinopathy. Diabetic retinopathy severity was categorized into non-proliferative diabetic retinopathy and proliferative diabetic retinopathy. Logistic regression model was used to evaluate the associations of diabetic retinopathy with pulse wave velocity and augmentation index. Results: Diabetic retinopathy was diagnosed in 391 (32.5%) patients, including 271 non-proliferative diabetic retinopathy and 108 proliferative diabetic retinopathy. Diabetic retinopathy have higher pulse wave velocity (11.2 ± 3.3 vs 9.5 ± 2.6 m/s, p < 0.001) and augmentation index (28.4 ± 9.4 vs 26.1 ± 10.6%, p < 0.001) than non-diabetic retinopathy. After multivariable adjustment, pulse wave velocity [odds ratio = 1.11 (95% confidence interval = 1.05–1.17), p < 0.001] and augmentation index [odds ratio = 1.03 (95% confidence interval = 1.01–1.04), p = 0.009] was associated with diabetic retinopathy. In severity analyses, pulse wave velocity was associated with non-proliferative diabetic retinopathy [odds ratio = 1.10 (95% confidence interval = 1.03–1.17), p = 0.002] and proliferative diabetic retinopathy [odds ratio = 1.15 (95% confidence interval = 1.06–1.25), p = 0.001] ( p-trend < 0.001). Augmentation index showed significant associations with non-proliferative diabetic retinopathy [odds ratio = 1.02 (95% confidence interval = 1.01–1.04), p = 0.008], but not with proliferative diabetic retinopathy [odds ratio = 1.01 (95% confidence interval = 0.98–1.04), p = 0.36] ( p-trend = 0.03). Conclusion: Central arterial stiffness was associated with the presence and severity of diabetic retinopathy in type 2 diabetes mellitus patients, suggesting its etiologic implication in diabetic retinopathy.


2020 ◽  
Vol 21 (24) ◽  
pp. 9558
Author(s):  
Vincenza Bonfiglio ◽  
Chiara Bianca Maria Platania ◽  
Francesca Lazzara ◽  
Federica Conti ◽  
Corrado Pizzo ◽  
...  

Transforming growth factor β1 (TGFβ1) is a proinflammatory cytokine that has been implicated in the pathogenesis of diabetic retinopathy (DR), particularly in the late phase of disease. The aim of the present study was to validate serum TGFβ1 as a diagnostic and prognostic biomarker of DR stages. Thirty-eight subjects were enrolled and, after diagnosis and evaluation of inclusion and exclusion criteria, were assigned to six groups: (1) healthy age-matched control, (2) diabetic without DR, (3) non-proliferative diabetic retinopathy (NPDR) naïve to treatment, (4) NPDR treated with intravitreal (IVT) aflibercept, (5) proliferative diabetic retinopathy (PDR) naïve to treatment and (6) PDR treated with IVT aflibercept. Serum levels of vascular endothelial growth factor A (VEGF-A), placental growth factor (PlGF) and TGFβ1 were measured by means of enzyme-linked immunosorbent assay (ELISA). Foveal macular thickness (FMT) in enrolled subjects was evaluated by means of structural-optical coherence tomography (S-OCT). VEGF-A serum levels decreased in NPDR and PDR patients treated with aflibercept, compared to naïve DR patients. PlGF serum levels were modulated only in aflibercept-treated NPDR patients. Particularly, TGFβ1 serum levels were predictive of disease progression from NPDR to PDR. A Multivariate ANOVA analysis (M-ANOVA) was also carried out to assess the effects of fixed factors on glycated hemoglobin (HbA1c) levels, TGFβ1, and diabetes duration. In conclusion, our data have strengthened the hypothesis that TGFβ1 would be a biomarker and pharmacological target of diabetic retinopathy.


2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Hui-Jin Chen ◽  
Zhi-Zhong Ma ◽  
Ying Li ◽  
Chang-Guan Wang

Purpose. To study the change of concentrations of vascular endothelial growth factor (VEGF) in vitreous cavity after vitrectomy in eyes with proliferative diabetic retinopathy (PDR). Methods. In this retrospective study, intravitreal fluid samples were taken at baseline (beginning of the vitrectomy) and postoperatively (several days later after vitrectomy) at the time of prophylactic injection of bevacizumab in forty-eight eyes of forty-eight patients with PDR. Postvitrectomy fluid samples were divided into four groups according to the time interval between the vitrectomy and the injection (group 1, 3–5 days; group 2, 6–10 days; group 3, 11–15 days; group 4, 16–21 days; twelve eyes in each group). Postvitrectomy fluid sample was paired with baseline sample for each eye. VEGF concentrations in the samples were determined by enzyme-linked immunosorbent assay. Recurrent vitreous hemorrhage and neovascular glaucoma within six months postvitrectomy were also analyzed. Results. Overall, the intravitreal VEGF level after vitrectomy (median, 36.95 pg/ml; range, 3.2–1,299.4 pg/ml) was significantly less than the VEGF level at baseline (median, 704.5 pg/ml; range, 30.6–1,981.1 pg/ml). Postoperative and baseline VEGF levels were significantly correlated (r = 0.499, p<0.01). Both the absolute value of postoperative VEGF concentrations and the postop/baseline VEGF ratios declined with time and dramatically decreased in groups 3 and 4. In only two eyes, the postoperative VEGF level was even higher than the baseline VEGF level (postop/baseline VEGF ratio >1), and recurrent vitreous hemorrhage developed within six months in these two eyes. Conclusions. After vitrectomy for PDR, intravitreal VEGF levels decreased substantially in the majority of patients, while persistent high-VEGF level occurred in a few individuals. Postoperative VEGF levels and postop/baseline VEGF ratio declined with time. The postop/preop VEGF ratio may serve as a predictor for late complications.


1995 ◽  
Vol 74 (04) ◽  
pp. 1045-1049 ◽  
Author(s):  
P Butthep ◽  
A Bunyaratvej ◽  
Y Funahara ◽  
H Kitaguchi ◽  
S Fucharoen ◽  
...  

SummaryAn increased level of plasma thrombomodulin (TM) in α- and β- thalassaemia was demonstrated using an enzyme-linked immunosorbent assay (ELISA). Nonsplenectomized patients with β-thalassaemia/ haemoglobin E (BE) had higher levels of TM than splenectomized cases (BE-S). Patients with leg ulcers (BE-LU) were found to have the highest increase in TM level. Appearance of larger platelets in all types of thalassaemic blood was observed indicating an increase in the number of younger platelets. These data indicate that injury of vascular endothelial cells is present in thalassaemic patients.


2019 ◽  
Author(s):  
Shangze Gao ◽  
Hidenori Wake ◽  
Masakiyo Sakaguchi ◽  
Dengli Wang ◽  
Youhei Takahashi ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hongseok Yoo ◽  
Yunjoo Im ◽  
Ryoung-Eun Ko ◽  
Jin Young Lee ◽  
Junseon Park ◽  
...  

AbstractThe role of high-mobility group box-1 (HMGB1) in outcome prediction in sepsis is controversial. Furthermore, its association with necroptosis, a programmed cell necrosis mechanism, is still unclear. The purpose of this study is to identify the association between the plasma levels of HMGB1 and the severity and clinical outcomes of sepsis, and to examine the correlation between HMGB1 and key executors of necroptosis including receptor-interacting kinase 3 (RIPK3) and mixed lineage kinase domain-like- (MLKL) proteins. Plasma HMGB1, RIPK3, and MLKL levels were measured with the enzyme-linked immunosorbent assay from the derivation cohort of 188 prospectively enrolled, critically-ill patients between April 2014 and December 2016, and from the validation cohort of 77 patients with sepsis between January 2017 and January 2019. In the derivation cohort, the plasma HMGB1 levels of the control (n = 46, 24.5%), sepsis (n = 58, 30.9%), and septic shock (n = 84, 44.7%) groups were significantly increased (P < 0.001). A difference in mortality between high (≥ 5.9 ng/mL) and low (< 5.9 ng/mL) HMGB1 levels was observed up to 90 days (Log-rank test, P = 0.009). There were positive linear correlations of plasma HMGB1 with RIPK3 (R2 = 0.61, P < 0.001) and MLKL (R2 = 0.7890, P < 0.001). The difference in mortality and correlation of HMGB1 levels with RIPK3 and MLKL were confirmed in the validation cohort. Plasma levels of HMGB1 were associated with the severity and mortality attributed to sepsis. They were correlated with RIPK3 and MLKL, thus suggesting an association of HMGB1 with necroptosis.


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