Proteomic Analysis of the Vitreous Body in Proliferative and Non-Proliferative Diabetic Retinopathy

2020 ◽  
Vol 17 ◽  
Author(s):  
Van-An Duong ◽  
Jeeyun Ahn ◽  
Na-Young Han ◽  
Jong-Moon Park ◽  
Jeong-Hun Mok ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Proliferative Diabetic Retinopathy ◽  
Microvascular Complications ◽  
Treatment Options ◽  
Vitreous Body ◽  
Control Group ◽  
Diabetic Patients ◽  
Protein Protein Interaction ◽  
Alpha Beta ◽  
New Treatment

Background: Diabetic Retinopathy (DR), one of the major microvascular complications commonly occurring in diabetic patients, can be classified into Proliferative Diabetic Retinopathy (PDR) and Non-Proliferative Diabetic Retinopathy (NPDR). Currently available therapies are only targeted for later stages of the disease in which some pathologic changes may be irreversible. Thus, there is a need to develop new treatment options for earlier stages of DR through revealing pathological mechanisms of PDR and NPDR. Objective: The purpose of this study was to characterize proteomes of diabetic through quantitative analysis of PDR and NPDR. Methods: Vitreous body was collected from three groups: control (non-diabetes mellitus), NPDR, and PDR. Vitreous proteins were digested to peptide mixtures and analyzed using LC-MS/MS. MaxQuant was used to search against the database and statistical analyses were performed using Perseus. Gene ontology analysis, related-disease identification, and protein-protein interaction were performed using the differential expressed proteins. Results: Twenty proteins were identified as critical in PDR and NPDR. The NPDR group showed different expressions of kininogen-1, serotransferrin, ribonuclease pancreatic, osteopontin, keratin type II cytoskeletal 2 epidermal, and transthyretin. Also, prothrombin, signal transducer and activator of transcription 4, hemoglobin subunit alpha, beta, and delta were particularly up-regulated proteins for PDR group. The up-regulated proteins related to complement and coagulation cascades. Statherin was down-regulated in PDR and NPDR compared with the control group. Transthyretin was the unique protein that increased its abundance in NPDR compared with the PDR and control group. Conclusion: This study confirmed the different expressions of some proteins in PDR and NPDR. Additionally, we revealed uniquely expressed proteins of PDR and NPDR, which would be differential biomarkers: prothrombin, alpha-2-HS-glycoprotein, hemoglobin subunit alpha, beta, and transthyretin.

The Level of Cytokines in the Vitreous Body of Severe Proliferative Diabetic Retinopathy Patients Undergoing Posterior Vitrectomy

2018 ◽  
Vol 24 (27) ◽  
pp. 3276-3281 ◽  
Author(s):  
Dorota Raczyńska ◽  
Katarzyna A. Lisowska ◽  
Krzysztof Pietruczuk ◽  
Joanna Borucka ◽  
Mateusz Ślizień ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Proliferative Diabetic Retinopathy ◽  
Vitreous Body ◽  
Control Group ◽  
Slit Lamp ◽  
Corrected Visual Acuity ◽  
Cytokine Levels ◽  
Pars Plana ◽  
Eye Examination

Objective: The objective of the study was to compare cytokine levels in the vitreous body of patients with proliferative diabetic retinopathy (PDR) undergoing posterior vitrectomy. Patients and methods: The study included 39 patients (39 eyes) undergoing pars plana vitrectomy (PPV). Patients were divided into three groups: patients with proliferative diabetic retinopathy (PDR) without aflibercept injection prior to the surgery, PDR patients administered aflibercept injection prior to the surgery, and patients without diabetes mellitus (control group). All patients underwent a comprehensive eye examination one day before and 3 weeks after the surgery, including measurements of: best-corrected visual acuity (BVCA) and intraocular pressure (IOP), slit-lamp examination and spectral domain optical coherence tomography (SOCT). Concentrations of cytokines: IL-6, IL-8, IL-12p70, TNF, IL-10, IL-1β were measured in the vitreous body of patients with BD™ Cytometric Bead Array (CBA) Human Inflammatory Cytokines Kit. Results: PDR patients who received pretreatment with aflibercept injection showed significantly lower concentrations of IL-12p70, TNF, IL-10 and IL-1β in the vitreous body compared to the control group. Meanwhile, patients without prior aflibercept injection had a significantly higher concentration of IL-8. There was also a significant positive correlation between IOP before PPV and IL-8 concentration in both PDR patients’ groups. Conclusion: Findings of our study suggest an important role of IL-8 in the development of severe PDR. Aflibercept administration on the day before elective vitrectomy facilitated the surgery.

scholarly journals Effects of Intra-vitreal Injection of Bevacizumab as an Adjunct during Phacoemulsification in Diabetic Maculopathy

2020 ◽  
Vol 37 (1) ◽  
Author(s):  
Ali Afzal Bodla ◽  
Syeda Minahil Kazmi ◽  
Noor Tariq ◽  
Ayema Moazzam ◽  
Muhammad Muneeb Aman
Keyword(s):  
Diabetic Retinopathy ◽  
Macular Edema ◽  
Proliferative Diabetic Retinopathy ◽  
Macular Thickness ◽  
Control Group ◽  
Key Words Diabetes Mellitus ◽  
Diabetic Patients ◽  
Key Words Diabetes ◽  
Post Surgery ◽  
Significant Difference

Purpose:  To study the effects of Intra-vitreal injection of Bevacizumab as an adjunct during phacoemulsification in patients with diabetic retinopathy. Study Design:  Quasi experimental study. Methods:  Hundred diabetic patients who were scheduled to undergo phacoemulsification were included in the study. They were equally divided into two groups; Bevacizumab and control group. Complete ocular examination and macular thickness and volume were determined using an OPTOVUE-OCT machine. The patients in the Bevacizumab group were given intra-vitreal injection of 1.25 mg/0.05ml of Bevacizumab at the time of Phacoemulsification. A written ethical approval was obtained and the study was conducted according to principles of declaration of Helsinki. Results:  The bevacizumab group manifested low value of CMT one month post-surgery as compared to the control group (262.2 ± 32.2 and 288.5 ± 54.1, respectively) with P = 0.01. The Total Macular volume, and Best-corrected visual acuity in the two groups showed no significant difference one month after surgery. Amongst the patients who developed postsurgical macular edema, four patients did not possess a positive history for diabetic retinopathy and 3 of them had Non Proliferative Diabetic Retinopathy. We found no significant relationship between the post-surgical macula edema with the presence of mild Non Proliferative Diabetic Retinopathy. (Fisher's test, P = 0.321). Conclusion:  The ocular anti-VEGF therapy substantially reduces macular edema secondary to post-surgical inflammation in diabetic patients. It effectively reduces the central macular thickness although the results are not found to be statistically significant when compared with the control group. Key Words:  Diabetes mellitus; diabetic macular edema; diabetic retinopathy: Bevacizumab.

The association of serum and vitreous adropin concentrations with diabetic retinopathy

2019 ◽  
Vol 56 (2) ◽  
pp. 253-258 ◽  
Author(s):  
Shipeng Li ◽  
Jianling Sun ◽  
Wenchao Hu ◽  
Yan Liu ◽  
Dan Lin ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Diabetic Retinopathy ◽  
Proliferative Diabetic Retinopathy ◽  
Assay Method ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Diabetic Patients

Objective Adropin, a newly identified regulatory protein encoded by Enho gene, is correlated with insulin sensitivity and diabetes. The aim of this study is to determine whether serum and vitreous adropin concentrations are correlated with the presence of diabetic retinopathy. Methods A population of 165 patients with type 2 diabetes mellitus (52 without diabetic retinopathy, 69 with non-proliferative diabetic retinopathy and 44 patients with proliferative diabetic retinopathy) was enrolled in this study. The control group enrolled 68 healthy subjects who had underwent vitrectomy for retinal detachment. Serum and vitreous adropin concentrations were examined using enzyme-linked immunosorbent assay method. Results Control subjects had significantly higher serum and vitreous adropin concentrations compared with diabetic patients. Serum and vitreous adropin concentrations in proliferative diabetic retinopathy patients were significantly reduced compared with those in non-proliferative diabetic retinopathy patients and type 2 diabetes mellitus patients without diabetic retinopathy. In addition, there were lower serum and vitreous adropin concentrations in non-proliferative diabetic retinopathy patients compared with type 2 diabetes mellitus patients without diabetic retinopathy. Logistic regression analysis revealed that serum and vitreous adropin were associated with a decreased risk of type 2 diabetes mellitus and diabetic retinopathy. Conclusion Serum and vitreous adropin concentrations are negatively associated with the presence of diabetic retinopathy.

scholarly journals Distribution of DD Genotype of Angiotensin-Converting Enzyme Gene and Its Correlation with Diabetic Retinopathy

2021 ◽  
Vol 1 (2) ◽  
Author(s):  
Hamid Ali-Bahar ◽  
Maysam Mard-Soltani ◽  
Yousef Paridar ◽  
Zahra Nasirbaghban ◽  
Zahra Sadat Hashemi ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Diabetic Retinopathy ◽  
Angiotensin Converting Enzyme ◽  
Microvascular Complications ◽  
Control Group ◽  
Case Group ◽  
Diabetic Patients ◽  
Converting Enzyme ◽  
Ace Gene ◽  
And Control

Background: One of the major microvascular complications of diabetes mellitus (DM) is diabetic retinopathy (DR). Studies have shown that angiotensin-converting enzyme (ACE) gene polymorphisms are correlated with DR progression. Accordingly, the elucidation of the association between ACE gene polymorphism and the risk of DR development seems to be highly crucial. Methods: In this study, 195 individuals with type 2 diabetes mellitus (T2DM) were classified as the case group with retinopathy (99 people) and control group without retinopathy (96 people). Screening for DR was performed by ophthalmologists using clinical examination and fluorescein angiography. Different ACE genotypes (II, ID, and DD) were identified by the collection of blood samples, extraction of DNA, and PCR amplification using specific primers. Results: The frequency distribution of genotypes was significantly different between the case and control groups (P = 0.009). Interestingly, possessing a DD genotype made diabetic patients approximately 2.5 folds (95% CI = 1.271 - 4.840, P = 0.007) and 3.25 folds (95% CI = 1.312 - 8.051, P = 0.01) more susceptible to DR when compared to having DI and II genotypes, respectively. Moreover, having a D allele made diabetic individuals nearly 1.75 folds (95% CI = 1.167 - 2.623, P = 0.007) more susceptible to DR than possessing an I allele. Conclusions: Our results potentiate the hypothesis that the DD genotype and D allele of the ACE gene might play a role in the pathogenesis of DR.

scholarly journals Systemic Erythropoietin Concentration and its Correlation with Stage of Diabetic Retinopathy

2019 ◽  
Author(s):  
Sofija Davidović ◽  
Babić Nikola ◽  
Jovanović Sandra ◽  
Barišić Sava ◽  
Grković Desanka ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Diabetic Retinopathy ◽  
Serum Concentration ◽  
Proliferative Diabetic Retinopathy ◽  
Elevated Serum ◽  
Average Concentration ◽  
Control Group ◽  
Diabetic Patients ◽  
Study Results ◽  
Patients With Diabetes

Abstract Summary: Background: Erythropoietin (Epo) is one of systemic angiogenic factors, and its role in ocular angiogenesis and in diabetic retinopathy (DR) is not yet fully understood. Latest research data reveal possible correlation of higher EPO concentrations of erythropoietin in blood and in the eye, with more severe of stages of DR. The main aim of this work was to examine the possible influence of serum concentrations of erythropoietin on the development and stages of diabetic retinopathy in patients with diabetes mellitus type 2. Methods: The research involved 90 patients examined at University Eye Clinic in Clinical Center of Vojvodina in Novi Sad, Serbia. First group comprised of 60 patients with diabetes mellitus lasting 10 years or more, with diabetic retinopathy. Second, control group, consisted of 30 healthy individuals. In the first group of 60 diabetic patients, 30 of them had non-proliferative diabetic retinopathy (NPDR), and 30 had proliferative diabetic retinopathy (PDR). Laboratory EPO serum levels were determined, and they were correlated to the stage of DR. Concentration of EPO was assessed by ELISA method at the end of the study. Results: The highest average concentration of EPO in serum (9.95 mIU/ml) was determined in group of diabetics with PDR. The lowest average concentration of EPO in serum (6.90 mIU/ml) was found in control group. The average concentration of Epo in serum in group of diabetics with NPDR was 7.00 mIU/ml. EPO concentration in serum was elevated in group of PDR, and it was directly proportional to the level of clinical stadium of PDR, being significantly higher in moderate and severe subgroup of PDR comparing to control healthy subjects, NPDR and mild PDR (h=9.858, p=0.007). Conclusions: Significantly elevated serum concentration of EPO in advanced stages of DR, and positive correlation between EPO serum concentration and clinical stadium of PDR, suggest that erythropoietin presents one of the important growth factors from blood, which plays role in retinal ischemia and angiogenesis in diabetic retinopathy, especially in the proliferative stage of this disease. Keywords: diabetic retinopathy; erythropoietin; glycated hemoglobin; non-proliferative diabetic retinopathy; proliferative diabetic retinopathy.

Results of Anti-VEGF Therapy in the Treatment of Post-vitrectomy Vitreous Hemorrhage in Patients with Proliferative Diabetic Retinopathy

2021 ◽  
pp. 97-103
Author(s):  
O. O. Putiienko
Keyword(s):  
Diabetic Retinopathy ◽  
Gas Exchange ◽  
Recurrence Rate ◽  
Proliferative Diabetic Retinopathy ◽  
Treatment Options ◽  
Vitreous Hemorrhage ◽  
Main Group ◽  
Control Group ◽  
Anti Vegf ◽  
Significant Difference

Post-vitrectomy vitreous hemorrhage in patients with proliferative diabetic retinopathy (PDR) occurs in up to 75% of cases, and this highlights the need to search for new treatment options. The aim. To analyze the results of anti-VEGF therapy in the treatment of post-vitrectomy vitreous hemorrhage in patients with PDR. Materials and methods. Seventy-eight patients (78 eyes) were examined. Twenty patients (20 eyes) of the control group underwent outpatient fluid gas exchange (OFGE) with 20% gas-air mixture of perfluoropropane for the treatment of post-vitrectomy vitreous hemorrhage. The first main group included 28 patients in whom OFGE with the same mixture was supplemented by the injection of Lucentis at a dose of 0.5 mg into the vitreous cavity. The second main group included 30 patients who achieved Eylea at a dose of 2 mg in addition to the OFGE. Results. Within 2 months, no significant difference between groups in achieving vitreous transparency or in vitreous hemorrhage recurrence rate was found. After 6 months, the frequency of vitreous hemorrhage recurrence in the control group was significantly higher (χ2 = 4.27; p = 0.039) than that in the Lucentis group (9 eyes [45%] vs. 3 eyes [10.7%]). When using Eylea in the same period, the recurrence rate was 6.7% (2 eyes) which is significantly lower than 45% (9 eyes) in the control group (χ2 = 4.59; p = 0.032). Conclusions. The effectiveness of treatment of post-vitrectomy vitreous hemorrhage by OFGE with 20% gas-air mixture of perfluoropropane within 6 months of observation is 85.5%. The use of Lucentis increases the effectiveness to 92.8% with a recurrence rate of 10.7%, and the use of Eylea to 96.6% with a recurrence rate of 6.7%. There are no significant differences between the use of Lucentis and Eylea. Keywords: proliferative diabetic retinopathy, post-vitrectomy vitreous hemorrhage, outpatient fluid gas exchange, Lucentis, Eylea.

scholarly journals TNF-Alpha Levels in Tears: A Novel Biomarker to Assess the Degree of Diabetic Retinopathy

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
C. Costagliola ◽  
V. Romano ◽  
M. De Tollis ◽  
F. Aceto ◽  
R. dell’Omo ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Diabetic Retinopathy ◽  
Body Mass ◽  
Proliferative Diabetic Retinopathy ◽  
Fluid Collection ◽  
Tnf Alpha ◽  
Control Group ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Necrosis Factor Alpha

We assess the level of tumour necrosis factor alpha (TNF-alpha) in tear fluids and other serum parameters associated with diabetes in different degrees of diabetic retinopathy. We have performed a prospective, nonrandomized, observational study. Study population consisted of 16 healthy subjects (controls) and 32 type 2 diabetic patients: 16 affected by proliferative diabetic retinopathy (PDR) and 16 with nonproliferative retinopathy (NDPR, background/preproliferative). Body mass index, urinary albumin, blood glucose, HbA1c, and tear levels of TNF-alpha were measured in all subjects. The value of glycaemia, microalbuminurea, and Body mass index in diabetic retinopathy groups were higher than those in control group (). Glycemia in NPDR: 6.6 mmol/L (range: 5.8–6.3); in PDR: 6.7 mmol/L (range: 6.1–7.2); in control: 5.7 mmol/L (range: 4.9–6.1); microalbuminurea in NPDR: 10.6 mg/L (range: 5.6–20); in PDR: 25.2 mg/L (range: 17–40); in control: 5.3 mg/L (range: 2.6–10); Body mass index in NPDR: 26 Kg/m2(range: 20.3–40); in PDR: 28 Kg/m2(range 20.3–52); in control: 21 Kg/m2(range 19–26). The TNF-alpha concentrations in tears increase with the severity of pathology and were lower in control group than in diabetic subjects. In the end, the level of TNF-alpha is highly correlated with severity of diabetic retinopathy and with nephropathy. Tear fluid collection may be a useful noninvasive method for the detection of proliferative diabetic retinopathy.

scholarly journals Anatomic and Topographic Vitreous and Vitreoretinal Interface Features in Proliferative Diabetic Vitreoretinopathy

2020 ◽  
Vol 17 (2) ◽  
pp. 249-257
Author(s):  
N. M. Kislitsyna ◽  
S. V. Novikov ◽  
S. V. Kolesnik ◽  
A. I. Kolesnik ◽  
M. P. Veselkova
Keyword(s):  
Diabetic Retinopathy ◽  
Proliferative Diabetic Retinopathy ◽  
Imaging Techniques ◽  
Posterior Vitreous Detachment ◽  
Vitreous Body ◽  
Diabetic Patients ◽  
Vitreoretinal Interface ◽  
Posterior Cortex ◽  
Vitreous Cortex

The role of the vitreous body and vitreomacular interface (VMI) is key in many processes including proliferative diabetic retinopathy (PDR). In PDR patients, the VMI changes can significantly influence the emergence and progression of the disease. There are multiple factors at work in the VMI including taut posterior cortical layers, vitreoschisis, posterior vitreous detachment (PVD), and vitreous adhesions. But there is no general consensus about their role in proliferative complications. Further understanding the VMI relationship in a case of PDR is warranted in order to design better treatments, to arrest and possibly even reverse progression of PDR.  Today there is no imaging techniques to determine normal vitreous and VMI interactions in different PDR stages intraoperatively. Purpose: to analyze intraoperative vitreous and vitreoretinal interface features during chromovitrectomy in patients with A-C stages of PDR. Patients and methods. Seventy-four diabetic patients (74 eyes) were included. We performed standard 25 Gauge pars plana vitrectomy using Vitreocontrast for vitreous and vitreoretinal interface (VRI) visualization. Intravitreal “Vitreocontrast” suspension is the most favored agent of those studied and it is increasingly used as an adjunct during surgery to delaminate fine tissue planes and pockets of formed vitreous and VRI structures that may not be visible with routine operative illumination systems, or using modern vital dyes. Results. “Vitreocontrast” suspension allows to visualize posterior cortex changes during different stages of PDR. We investigated vitreous and VRI anatomy, topography and structure and determined safety of retrociliary and equatorial cisterns walls in 97 % in stage A of PDR, 95 % in stage B and in 82 % of stage C. In 3–5–18 % cases, correspondently, we determined disorganization of some vitreous cisterns. In 94 % cases of PDR A and 96 % cases of PDR B we visualized preretinal vitreous layer in a central macular zone, within the boundaries of vascular arcades. It has specific topography and strong adhesion to the internal retinal membrane. It’s the first time when this new vitreous cortex layer was revealed. The presence of this layer is the result of a strong vitreomacular adhesion that causes the posterior vitreous cortex split as it attempts to detach from the inner retinal surface. Such outermost layer remains attached to the macula and can induce further proliferation process. On a stage B of PDR this area correspond with multiple vitreoschisis, on a stage C of PDR — with fibrovascular membrane. The complete PVD was revealed in 61 cases. Conclusion. In this article we analyze the results of surgical treatment in 74 patients with A-C stages of proliferative diabetic retinopathy. Newer imaging technique with new dye — suspension “Vitreocontrast” allows to detect sensitive relationships of vitreous and VRI in each stage of the disease. The role of vitreous body in this process gives us a reason to consider it as an important object for further research. Moreover, the understanding of their relations in different stages of PDR enables to develop optimal surgical approach on each stage of PDR.

scholarly journals Reduced Expression of Erythropoietin After Intravitreal Ranibizumab in Proliferative Diabetic Retinopathy Patients—Retrospective Interventional Study

2021 ◽  
Vol 8 ◽  
Author(s):  
Li Chen ◽  
Jing Feng ◽  
Yanhong Shi ◽  
Fuxiao Luan ◽  
Fang Ma ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Proliferative Diabetic Retinopathy ◽  
Diagnostic Value ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Diabetic Patients ◽  
Intravitreal Ranibizumab ◽  
Epiretinal Membranes ◽  
Significant Difference ◽  
Endothelial Growth Factor

Purpose: To evaluate the expressions of erythropoietin (EPO) and vascular endothelial growth factor (VEGF) in the vitreous and fibrovascular membranes (FVMs) of proliferative diabetic retinopathy (PDR) after the intravitreal injection of ranibizumab (IVR) and further explore the relationship between EPO and VEGF.Method: The concentrations of EPO and VEGF levels in the vitreous fluid were measured in 35 patients (24 PDR and 11 non-diabetic patients) using enzyme-linked immunosorbent assay. The patients were divided into three groups: PDR with IVR (IVR group) before par plana vitrectomy (n = 10), PDR without IVR (Non-IVR group) (n = 14) and a control group [macular holes (MHs) or epiretinal membranes (ERM), n = 11]. Fluorescence immunostaining was performed to examine the expressions of VEGF, EPO and CD 105 in the excised epiretinal membranes.Result: The PDR eyes of Non-IVR group had the highest vitreous VEGF and EPO levels (836.30 ± 899.50 pg/ml, 99.29 ± 27.77 mIU/ml, respectively) compared to the control group (10.98 ± 0.98 pg/ml and 18.96 ± 13.30 mIU/ml/ml). Both the VEGF and EPO levels in the IVR group (13.22 ± 2.72 pg/ml and 68.57 ± 41.47 mIU/ml) were significantly lower than the Non-IVR group (P = 0.004 and P = 0.04, respectively). Furthermore, no significant difference was observed for VEGF levels between the control and IVR groups (10.9 ± 0.98 pg/ml and 13.22 ± 2.72 pg/ml, respectively, P = 0.9). Yet the EPO level in the IVR group was significantly higher than that in the Non-diabetic group (68.57 ± 41.47 pg/ml and 18.96 ± 13.30 pg/ml, respectively, P = 0.001). The expressions of EPO, VEGF, and CD105 were significantly reduced in fluorescence immunostaining of FVMs in the IVR group compared with the Non-IVR group. The receiver operating characteristic (ROC) curve of the EPO and VEGF levels were 0.951 and 0.938 in the PDR group.Conclusion: Both of the VEGF and EPO level were significantly increased in PDR patients, which have equal diagnostic value in the prediction of PDR. IVR could reduce the EPO level, but not enough to the normal level.

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