scholarly journals Correlations Between Different Angiogenic and Inflammatory Factors in Vitreous Fluid of Eyes With Proliferative Diabetic Retinopathy

2021 ◽  
Vol 8 ◽  
Author(s):  
Guanrong Wu ◽  
Baoyi Liu ◽  
Qiaowei Wu ◽  
Changting Tang ◽  
Zijing Du ◽  
...  

Purpose: To investigate the expression of various angiogenesis and inflammation mediators in the vitreous fluid of eyes with proliferative diabetic retinopathy (PDR).Methods: A total of 38 eyes with PDR and 37 control eyes were included. Vitreous fluid was collected during vitrectomy. Vitreous levels of colony stimulating factor-1 receptor (CSF-1R), syndecan-1, placental growth factor (PIGF), and angiopoietin-like protein 4 (ANGPTL-4) were measured by multiplex immunoassay. Vitreous levels of vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), interleukin-8 (IL-8), monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), and intercellular adhesion molecule-1 (ICAM-1) were measured by cytometric beads array. Levels of these mediators were compared between the PDR and control eyes. Correlations between levels of different mediators and between these mediators and kidney function metrics in the PDR group were also analyzed.Results: Vitreous levels of syndecan-1, PIGF, ANGPTL-4, VEGF, and IL-8 were significantly higher in the PDR group compared to the control group (all p < 0.05). Levels of VEGF were significantly correlated with levels of syndecan-1, PIGF, and ANGPTL-4 (r = 0.370 to 0.497, all p < 0.05). Significant positive correlations were detected between levels of any two of the following mediators including syndecan-1, PIGF, ANGPTL-4, and IL-8 (r = 0.370 to 0.906, all p < 0.05). Apart from VEGF, levels of these mediators were positively correlated with serum creatinine and blood urea nitrogen (r = 0.328 to 0.638, all p < 0.05), and negatively correlated with fasting blood glucose and estimated glomerular filtration rate (r = −0.325 to −0.603, all p < 0.05).Conclusions: Correlations between different angiogenesis and inflammation mediators were observed in eyes with PDR, suggesting cross-talks of different angiogenesis and inflammation pathways in the pathogenesis of PDR. The levels of angiogenesis and inflammation in PDR are correlated with kidney damage, indicating possible common pathways in diabetic retinopathy and nephropathy.

Author(s):  
Ressa Yuneta ◽  
Tjahjono Darminto Gondhowiardjo ◽  
Rahayuningsih Dharma ◽  
Sri Widia A. Jusman ◽  
Joedo Prihartono ◽  
...  

Purpose: to assess the levels of Hypoxia-inducible factor-1α (HIF-1α) and intercellular adhesion molecule-1 (ICAM-1) in vitreous of proliferative diabetic retinopathy patients which were given intravitreal bevacizumab (IVB), as well as its relation to the central macular thickness (CMT) measured prior to vitrectomy. Methods: thirty-two eyes were randomized into two groups, one that received an IVB injection at 1-2 weeks previtrectomy and the control group which did not receive any injection. Measurement of HIF-1α and ICAM-1 was conducted using enzyme-linked immunosorbent assay (ELISA). The CMT were measured at the initial visit, prior to vitrectomy, and at follow up time (2, 4, and 12 weeks postoperatively) using Stratus OCT. Results: The mean levels of HIF-1α vitreous (ng/mg protein) in the control group and IVB respectively 0.020 (0.006; 0.077) and 0.029 (0.016; 0.21). Vitreous levels of ICAM-1 (ng /mL) in control group and IVB group were 20.10 (3.41; 40.16) and 23.33 (0.63; 68.5). The mean levels of HIF-1α and ICAM-1 vitreous obtained did not differ significantly between the two groups. Conclusion: The levels of HIF-1α and ICAM-1 in PDR patients do not decrease after one injection of intravitreal Bevacizumab 1-2 weeks prior to vitrectomy. The concentration of vitreous HIF-1α and ICAM-1 are not directly related to the CMT.


PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0259683
Author(s):  
Hyun Seung Yang ◽  
Young Je Choi ◽  
Hee Yong Han ◽  
Hak Su Kim ◽  
So Hyun Park ◽  
...  

Purpose To compare adiponectin (APN) levels in the serum and aqueous humor (AH) and evaluate their association with the development/progression of diabetic retinopathy (DR). Methods Diabetic patients with (group 3; n = 59) and without (group 2; n = 39) DR and age- and sex-matched normal subjects (group 1; n = 35) were compared. Duration of diabetes, body mass index, serum HbA1c, vascular endothelial growth factor (VEGF), APN, pentraxin 3 (PTX3), platelet derived growth factor (PDGF), intercellular adhesion molecule-1 (ICAM-1), and APN were measured and analyzed. Results One hundred and thirty-three participants were included. Compared to patients without diabetes, diabetic patients with DR had significantly elevated average serum APN levels (5.99±3.89 μg/ml versus 3.51±1.44 μg/ml, P = 0.002) and average AH APN levels (10.94±11.74 ng/ml versus 3.65±3.33 ng/ml, P<0.001). Serum APN was significantly correlated with AH APN (R = 0.512, P<0.001) and AH VEGF (R = 0.202, P = 0.020). The log serum APN was significantly correlated with intraocular cytokines, including log APN, log VEGF, log ICAM, log leptin, log PTX3, log PDGF, angiopoietin, C-reactive protein, and interleukins (IL)-5 and IL-10 (P<0.001, P = 0.020, P<0.001, P<0.001, P = 0.001, P<0.001, P = 0.008, P = 0.009, P<0.001, and P = 0.046, respectively). Log serum VEGF showed a significant correlation only with log AH VEGF (P = 0.001). Multivariate logistic analysis was performed to evaluate the association of DR progression and cytokine concentrations; log Serum APN and log AH APN showed good correlation with the DR progression in each model. Conclusions AH APN levels correlated well with DR development and progression. Serum APN could be a better marker for estimating intraocular cytokines, including both intraocular APN and VEGF concentrations in clinical field, than serum VEGF in DR patients.


2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Stepan Rusnak ◽  
Jindra Vrzalova ◽  
Marketa Sobotova ◽  
Lenka Hecova ◽  
Renata Ricarova ◽  
...  

Purpose. To determine the intraocular levels of growth factors and cytokines in patients with various degrees of severity of proliferative diabetic retinopathy (PDR) using multiplex xMAP technology.Methods. A prospective cohort study of 61 eyes from 56 patients who were divided into 3 groups based on the severity of PDR. Patients in group number 1 are those who presented PDR with no need of repeated surgical intervention; patients in group number 2 had repeated vitreous bleeding; and patients in group number 3 had refractory neovascular glaucoma. The concentrations of proangiogenic, antiangiogenic, inflammatory, and neurotrophic factors were measured in intraocular fluid. The results were also compared with levels of factors measured in 50 eyes from 50 patients prior to senile cataract surgery (control group).Results. Patients with refractory neovascular glaucoma (the highest clinical severity group) had higher levels of interleukin 6 (IL-6) (median1 37.19; median3 384.74;P=.00096), transforming growth factor beta 1 (TGFβ-1) (median1 49.00; median3 414.40;P=.0017), and vascular endothelial growth factor (VEGF) (median1 211.62; median3 352.82;P=.0454) compared with other PDR patients.Conclusions. Results of our study imply that levels of IL-6, TGFβ-1, and VEGF correlate with the severity of PDR.


2003 ◽  
Vol 104 (3) ◽  
pp. 223-230 ◽  
Author(s):  
Rafael SIMÓ ◽  
Cristina HERNÁNDEZ ◽  
Rosa M. SEGURA ◽  
José GARCÍA-ARUMÍ ◽  
Laura SARAROLS ◽  
...  

The aim of the study was to evaluate the vitreous levels of free insulin-like growth factor 1 (IGF-1) in patients with proliferative diabetic retinopathy (PDR). For this, a total of 36 diabetic patients with PDR (group A) and 28 non-diabetic patients (group B) in whom a vitrectomy was performed were compared. Both groups were matched by age, sex and serum-free IGF-1. In a subgroup of diabetic patients (n = 21) and non-diabetic patients (n = 13), vitreous and serum total IGF-1, IGF-binding protein 1 (IGFBP-1) and IGFBP-3 were also determined. Serum and vitreous levels of free IGF-1, total IGF-1, IGFBP-1 and IGFBP-3 were measured by immunological methods. Vitreal proteins were assessed by a turbidimetric method and adjusted for vitreous haemoglobin. Vitreous levels of free IGF-1 were elevated in group A (median, 0.16ng/ml; range 0.06–0.57ng/ml) in comparison with group B (median, 0.12ng/ml; range 0.06–0.22ng/ml; P<0.001); however, after adjusting for vitreal proteins, free IGF-1 levels were significantly lower in group A in comparison with group B [0.05ng/mg (0.01–0.45ng/mg) versus 0.15ng/mg (0.07–0.66ng/mg); P<0.001]. The relatively lower free IGF-1 level observed in group A could not be attributed to differences in the distribution of intravitreous IGFBP-1 and IGFBP-3 in relation to total IGF-1. Notably, the contribution of free IGF-1 to total IGF-1 in vitreous fluid was 10% in group A and 42% in group B; these percentages largely exceed that obtained in serum (<1%). Our results suggest that although there is an enhancement of intravitreous free IGF-1 in diabetic patients due to serum diffusion, a deficit in its intraocular production also exists. In addition, these findings support the concept that intraocular-produced free IGF-1 plays a relevant role in retinal homoeostasis.


PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0248439
Author(s):  
Svenja Deuchler ◽  
Ralf Schubert ◽  
Pankaj Singh ◽  
Adonis Chedid ◽  
Natallia Brui ◽  
...  

Diabetic retinopathy (DR) is an inflammatory condition that affects the posterior of the eye; yet, there are limited published data on techniques measuring the expression of growth and inflammatory factors (GIF) from the posterior segment. The purpose of the current study was two-fold: to sample the vitreous fluid from the eyes of patients with DR and assess the expression of GIF. As DR is an inflammatory disease, the second objective of this study was to determine the relationship between the status of DR and the expression of vitreous GIF. This non-randomized clinical trial was approved by BfARM for the analysis and evaluation of 12 eyes from patients with diabetic macular edema. Vitreous sampling was performed before treatment with fluocinolone acetonide and the extracted vitreous material was examined for the determination of GIF including interleukins 6 (IL-6) and 8 (IL-8), interferon gamma-inducible protein (IP-10), monocyte chemoattractant protein-1 (MCP-1), placental growth factor (PIGF), pigment epithelium-derived factor (PEDF), VEGF (vascular endothelial growth factor) and intercellular adhesion molecule (CD54). These were linearly compared with the grade of inflammation in the vitreous assessed via DR score and ART. Additionally, all eyes were grouped based on their diabetic retinopathy status. All cytokine levels, except MCP-1 and PEDF, were numerically higher in DME patients with proliferative DR than those with non-proliferative DR. DR grade was found to linearly correlate with the expression of CD54 (p = 0.02, rho = 0.64), IL-8 (p = 0.03, rho = 0.64) and PIGF (p = 0.007, rho = 0.76). A correlation was found between ART and CD54 (p = 0.02, rho = 0.66) and also between ART and IL-8 (p = 0.04, rho = 0.60). A trend was found between ART and PIGF (p = 0.08, rho 0.52). For IL-6, there appeared to be a trend with DR grade (p = 0.14, rho = 0.45) and ART (p = 0.09, rho = 0.51). Proliferative DR was shown to be associated with a significant higher expression of CD54, IL-8 and PIGF, thus suggesting that they are potentially important in defining and monitoring the effectiveness of a patients’ therapy. Vitreous probes may be helpful in deciding which therapy to administer (i.e. anti-VEGF or corticosteroid or both) based on the expression of GIF. Registry EudraCT number: 2016-004488-38; DRKS-ID: DRKS00014915.


2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Neveen Salem ◽  
Nawal Helmi ◽  
Naglaa Assaf

Platelet-rich plasma (PRP) has grown as an attractive biologic instrument in regenerative medicine for its powerful healing properties. It is considered as a source of growth factors that may induce tissue repairing and improve fibrosis. This product has proven its efficacy in multiple studies, but its effect on cisplatin-induced nephrotoxicity has not yet been elucidated. The present investigation was performed to estimate the protective impact of platelet-rich plasma against cisplatin- (CP-) evoked nephrotoxicity in male rats. Nephrotoxicity was induced in male Wistar rats by right uninephrectomy followed by CP administration. Uninephrectomized rats were assigned into four groups: (1) control group, (2) PRP group, (3) CP group, and (4) CP + PRP group. PRP was administered by subcapsular renal injection. Renal function, inflammatory cytokines, and growth factor level as well as histopathological investigation were carried out. Treatment with PRP attenuated the severity of CP-induced nephrotoxicity as evidenced by suppressed creatinine, blood urea nitrogen (BUN), and N-acetyl glucosaminidase (NAG) levels. Moreover, PRP depressed intercellular adhesion molecule-1 (ICAM-1), kidney injury molecule-1 (KIM-1), caspase-3, and transforming growth factor-beta 1 (TGF-β1) levels, while enhanced the epidermal growth factor (EGF) level. These biochemical results were reinforced by the histopathological investigation, which revealed restoration of normal renal tissue architectures. These findings highlight evidence for the possible protective effects of PRP in a rat model of CP-induced nephrotoxicity, suggesting a new avenue for using PRP to improve the therapeutic index of cisplatin.


2019 ◽  
Vol 43 (1) ◽  
pp. 105
Author(s):  
Arnila Novitasari Saubig ◽  
Arief Wildan ◽  
Afrisal Hari Kurniawan

Introduction: to compare the levels of Placenta Growth Factor in the vitreous on patients with proliferative diabetic retinopathy at Aflibercept administration with control. Method: This is a prospective experimental study with post-test with control design. Subjects were taken from 24 eyes from 24 patients, who came to dr. Kariadi General Hospital and National Diponegoro Hospital between March until September 2016. Subjects were divided into the patient with Aflibercept administration and control. Study variables in this study are Placenta Growth Factor levels in the vitreous in the patient with diabetic proliferative retinopathy. Measurements of PlGF levels with ELISA methods are conducted at GAKI Laboratory, Medical Faculty, Diponegoro University. This data tested for normality used with Saphiro Wilk, and homogeneity variance with Lavene and test hypothesis used with Mann Whitney. Results: Sample of this study are 24 patients proliferative diabetic retinopathy, twelve are the control group, and twelve are Aflibercept group. Average levels of PlGF in the control group are 263,97 pg/ml + 354,98 SD, with minimum value 12,19 pg/ml and maximum value 1002,00 pg/ml. Average levels of PlGF in the treatment group are 92,84 pg/ml + 9,54 SD, with minimum value 76,45 pg/ml and maximum value 112,30 pg/ml. Hypothesis test results obtained significance value 0,488. Conclusion: There was no significant difference between PlGF levels in the control group and the treatment group.


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