scholarly journals Elevated Glucose and Interleukin-1β Differentially Affect Retinal Microglial Cell Proliferation

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Filipa I. Baptista ◽  
Célia A. Aveleira ◽  
Áurea F. Castilho ◽  
António F. Ambrósio
Keyword(s):  
Cell Proliferation ◽  
Diabetic Retinopathy ◽  
Cell Cultures ◽  
High Glucose ◽  
Neural Cell ◽  
Microglia Activation ◽  
Retinal Cell ◽  
Diabetic Patients ◽  
Low Grade ◽  
Activated State

Diabetic retinopathy is considered a neurovascular disorder, hyperglycemia being considered the main risk factor for this pathology. Diabetic retinopathy also presents features of a low-grade chronic inflammatory disease, including increased levels of cytokines in the retina, such as interleukin-1 beta (IL-1β). However, how high glucose and IL-1β affect the different retinal cell types remains to be clarified. In retinal neural cell cultures, we found that IL-1β and IL-1RI are present in microglia, macroglia, and neurons. Exposure of retinal neural cell cultures to high glucose upregulated both mRNA and protein levels of IL-1β. High glucose decreased microglial and macroglial cell proliferation, whereas IL-1β increased their proliferation. Interestingly, under high glucose condition, although the number of microglial cells decreased, they showed a less ramified morphology, suggesting a more activated state, as supported by the upregulation of the levels of ED-1, a marker of microglia activation. In conclusion, IL-1β might play a key role in diabetic retinopathy, affecting microglial and macroglial cells and ultimately contributing to neural changes observed in diabetic patients. Particularly, since IL-1β has an important role in retinal microglia activation and proliferation under diabetes, limiting IL-1β-triggered inflammatory processes may provide a new therapeutic strategy to prevent the progression of diabetic retinopathy.

Thiamine pyrophosphate diminishes nitric oxide synthesis in endothelial cells

2020 ◽  
pp. 1-9
Author(s):  
Susana Alcázar-Leyva ◽  
Estrella Zapata ◽  
Demetrio Bernal-Alcántara ◽  
Patricia Gorocica ◽  
Noé Alvarado-Vásquez
Keyword(s):  
Nitric Oxide ◽  
Cell Proliferation ◽  
Endothelial Cells ◽  
High Glucose ◽  
Thiamine Pyrophosphate ◽  
Diabetic Patients ◽  
Protective Agent ◽  
Nitric Oxide Synthesis ◽  
Umbilical Cord Vein ◽  
Cells Cultured

Abstract. Although thiamine pyrophosphate (TPP) is considered a protective agent for endothelial cells, it is still unknown if this is associated with nitric oxide (NO) synthesis. Our aim was to evaluate the synthesis of NO in endothelial cells incubated with TPP and high glucose concentrations. Endothelial cells from the umbilical cord vein from newborns (n = 20), were incubated with 5, 15 or 30 mmol/L glucose, in absence or presence of 0.625 mg/ml of TPP. Our results showed a significant increase in cell proliferation (> 40%; P < 0.05), and cell viability (> 90%; P < 0.001) after 48 h in endothelial cells cultured with glucose plus TPP. Likewise, in the presence of glucose and TPP an important rise in the consumption of glucose by the endothelial cells was observed after 24 h (> 7%; P < 0.001) and 48 h (> 10%; P < 0.05). Additionally, the levels of lactate after incubation with glucose and TPP showed only slight variations after 48 h (P < 0.05). However, these changes were clearly different from those observed in the absence of TPP. Interestingly, we found that the changes mentioned were linked with reduced levels of nitrites both at 24 h (< 171 pmol/μg protein; P < 0.001), and 48 h (< 250 pmol/μg protein; P < 0.05), which was associated with a reduced expression of mRNA of eNOS in endothelial cells incubated with TPP and high glucose. In conclusion, the presence of TPP regulates the consumption of glucose and the synthesis of NO, which would explain its protective effect in the endothelium of diabetic patients.

scholarly journals The Expression and Significance of mTORC1 in Diabetic Retinopathy

2019 ◽  
Author(s):  
Yanli Liu ◽  
Yarong Zheng ◽  
Yekai Zhou ◽  
Yi Liu ◽  
Mengjuan Xie ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Diabetic Retinopathy ◽  
Western Blotting ◽  
Rat Model ◽  
High Glucose ◽  
Control Group ◽  
Diabetes Group ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background: To investigate the expression and significance of mechanistic target of rapamycin complex 1(mTORC1) in diabetic retinopathy(DR), and to find new targets and new methods for the treatment of DR.Methods: A DR rat model was prepared by general feeding combined with intraperitoneal injection of 10% streptozotocin (60 mg/kg). The rats were randomly divided into a control group (NDM group) and diabetes group (DM group).Three months later,the degrees of retinopathy were determined using hematoxylin and eosin staining,and the levels of p-S6, VEGF, and PEDF proteins were detected by immunohistochemistry and western blotting. Human retinal capillary endothelial cells (HRCECs) were cultured in high glucose conditions,then treated with rapamycin or transfected with siTSC1.The protein levels of p-S6 were assessed by western blotting. The 5-ethynyl-2´-deoxyuridine assay was used to detect cell proliferation, and the Transwell assay was used to detect cell migration.Results: A DM rat model was successfully developed. The expressions of p-S6 and VEGF proteins were significantly increased in the DM group (p < 0.05), and the expression of PEDF protein was significantly decreased compared with the control group (p < 0.05). In vitro,the p-S6 protein in high glucose(HG) induced HRCECs was increased compared with the normal control (p < 0.05), and cell proliferation and migration were increased compared with the normal glucose(NG) group (p < 0.05). After transfection with siTSC1 to activate mTORC1,the expression of p-S6 was increased,as well as cell proliferation and migration.In contrast rapamycin decreased p-S6 expression in HG induced HRCECs, as well as decrased proliferation and migration (p < 0.05).Conclusion: The mTORC1 played an important role in DR. After activation, mTORC1 induced expression of the p-S6 protein, regulated the expressions of VEGF and PEDF proteins, and changed the proliferation and migration of endothelial cells.The mTORC1 can therefore be used as a new target,as well as in the treatment of DR.

Effect of Silencing Information Regulator on Islet β Cells in High Glucose Environment Through Regulation of Phosphatidylinositol 3 Kinase (PI3K)/Protein Kinase B (AKT)/Nuclear Factor-κ-Gene Binding Pathway

2021 ◽  
Vol 11 (8) ◽  
pp. 1624-1629
Author(s):  
Nali Liu ◽  
Beijing Zhu ◽  
Xin Wei
Keyword(s):  
Cell Proliferation ◽  
Insulin Secretion ◽  
High Glucose ◽  
Islet Cell ◽  
Control Group ◽  
Diabetic Patients ◽  
Phosphatidylinositol 3 Kinase ◽  
Sod Activity ◽  
Sirt1 Expression ◽  
Cell Supernatant

Islet β-cell regeneration is beneficial for treating diabetic patients. Silencing information regulator (SIRT1) has a regulatory role in endocrine diseases. However, SIRT1’s role in islet β cells remains unclear. MIN6 cells were cultured and assigned into control group, high glucose group, and SIRT1 group (treated with SIRT1 agonist, Resveratrol) followed by analysis of SIRT1 expression by Real time PCR and ELISA, cell proliferation by MTT assay, apoptosis activity by Caspase3 activity kit, secretion of TNF-α and IL-2 by ELISA, insulin secretion, ROS and SOD generation and expression of PI3K/Akt/NF-κB signaling by Western blot. SIRT1 mRNA was decreased in high glucose environment and its secretion in cell supernatant was reduced, with inhibited cell proliferation, increased Caspase3 activity and secretion of TNF-α and IL-2, decreased insulin secretion and SOD activity, increased ROS content, pAKT phosphorylation and NF-κB expression. Resveratrol significantly promoted SIRT1 expression and cell proliferation, decreased Caspase3 activity and secretion of TNF-α and IL-2, increased insulin secretion and SOD activity, as well as decreased ROS content, pAKT phosphorylation and NF-κB expression (P <0.05). SIRT1 is decreased in high glucose environment, and SIRT1 expression can inhibit islet cell apoptosis, inhibit oxidative stress and inflammation, and promote islet cell proliferation and insulin secretion by regulating PI3K/Akt/NF-κB signaling.

scholarly journals Intravitreal injection of adenosine A2A receptor antagonist reduces neuroinflammation, vascular leakage and cell death in the retina of diabetic mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Inês Dinis Aires ◽  
Maria Helena Madeira ◽  
Raquel Boia ◽  
Ana Catarina Rodrigues-Neves ◽  
Joana Margarida Martins ◽  
...  
Keyword(s):  
Cell Death ◽  
Diabetic Retinopathy ◽  
Intravitreal Injection ◽  
Therapeutic Potential ◽  
Ganglion Cells ◽  
Major Complication ◽  
Cell Loss ◽  
Vascular Leakage ◽  
Retinal Cell ◽  
Low Grade

AbstractDiabetic retinopathy is a major complication of diabetes mellitus and a leading cause of blindness. The pathogenesis of diabetic retinopathy is accompanied by chronic low-grade inflammation. Evidence shows that the blockade of adenosine A2A receptors (A2AR) affords protection to the retina through the control of microglia-mediated neuroinflammation. Herein, we investigated the therapeutic potential of an antagonist of A2AR in a model of diabetic retinopathy. Type 1 diabetes was induced in 4–5 months old C57BL/6 J mice with a single intraperitoneal injection streptozotocin. Animals were treated one month after the onset of diabetes. The A2AR antagonist was delivered by intravitreal injection once a week for 4 weeks. Microglia reactivity and inflammatory mediators were increased in the retinas of diabetic animals. The treatment with the A2AR antagonist was able to control microglial reactivity and halt neuroinflammation. Furthermore, the A2AR antagonist rescued retinal vascular leakage, attenuated alterations in retinal thickness, decreased retinal cell death and the loss of retinal ganglion cells induced by diabetes. These results demonstrate that intravitreal injection of the A2AR antagonist controls inflammation, affords protection against cell loss and reduces vascular leakage associated with diabetes, which could be envisaged as a therapeutic approach for the early complications of diabetes in the retina.

scholarly journals An Evaluation Based on Diabetic Retinopathy

2021 ◽  
Author(s):  
Simran Kaur ◽  
Barjinder Singh Saini
Keyword(s):  
Image Processing ◽  
Diabetic Retinopathy ◽  
Glucose Level ◽  
High Glucose ◽  
Diabetic Patients ◽  
High Glucose Level

Diabetic retinopathy is a globally rising disease and needs to be taken in concern. It is the problem with vision of diabetic patients due to a disease in the retina of diabetic patients.Diabetic patients have high glucose level in the blood.Our major concern is to predict the disease at early stages.The studies focusses on the modern techniques used in image processing digitally.It also puts a stress on patches classification used for the examination and prediction of diabetic retinopathy and judge the accuracy,senstivity of dataset.

scholarly journals Differentially Expressed MicroRNAs in the Development of Early Diabetic Retinopathy

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Qiaoyun Gong ◽  
Jia’nan Xie ◽  
Yang Liu ◽  
Ying Li ◽  
Guanfang Su
Keyword(s):  
Diabetic Retinopathy ◽  
High Glucose ◽  
Retinal Pigment ◽  
Treatment Strategies ◽  
Diabetic Rats ◽  
Retinal Cell ◽  
Rpe Cells ◽  
Hoechst Staining

The pathological mechanisms of diabetic retinopathy (DR), a leading cause of blindness in adults with diabetes mellitus, remain incompletely understood. Because microRNAs (miRNAs) represent effective DR therapeutic targets, we identified aberrantly expressed miRNAs associated with cellular dysfunction in early DR and detected their potential targets. We exposed human retinal endothelial cells (HRECs) and a cell line of retinal pigment epithelial (RPE) cells to high glucose (25 mmol/L, 1–7 days) to mimic DR progression and used streptozotocin-injected rats (4–8 weeks) for an in vivo diabetes model. HREC/RPE viability decreased after 24 h incubation and diminished further over 6 days, and Hoechst staining revealed hyperglycemia-induced HREC/RPE apoptosis. Although miR-124/-125b expression decreased with DR progression in vitro and in vivo, miR-135b/-199a levels decreased in retinal cells under hyperglycemia exposure, but increased in diabetic retinas. Moreover, miR-145/-146a expression decreased gradually in high-glucose-treated HRECs, but increased in hyperglycemia-exposed RPE cells and in diabetic rats. Our findings suggested that aberrant miRNA expression could be involved in hyperglycemia-induced retinal-cell dysfunction, and the identified miRNAs might vary in different retinal layers, with expression changes associated with DR development. Therefore, miRNA modulation and the targeting of miRNA effects on transcription factors could represent novel and effective DR-treatment strategies.

Targeting Matrix Metalloproteinases for Diabetic Retinopathy: The Way Ahead?

2019 ◽  
Vol 20 (4) ◽  
pp. 324-333 ◽  
Author(s):  
Ankita Solanki ◽  
Lokesh K. Bhatt ◽  
Thomas P. Johnston ◽  
Kedar S. Prabhavalkar
Keyword(s):  
Diabetic Retinopathy ◽  
Matrix Metalloproteinases ◽  
Mitochondrial Dysfunction ◽  
Retinal Cell ◽  
Diabetic Patients ◽  
Oxygen Species ◽  
Physiological Conditions ◽  
Pathological Conditions ◽  
Species Production ◽  
Acellular Capillaries

Diabetic retinopathy (DR) is a severe sight-threatening complication of diabetes. It causes progressive damage to the retina and is the most common cause of vision impairment and blindness among diabetic patients. DR develops as a result of various changes in the ocular environment. Such changes include accelerated mitochondrial dysfunction, apoptosis, reactive oxygen species production, and formation of acellular capillaries. Matrix metalloproteinases (MMPs) are one of the major culprits in causing DR. Under physiological conditions, MMPs cause remodeling of the extracellular matrix in the retina, while under pathological conditions, they induce retinal cell apoptosis. This review focuses on the roles of various MMPs, primarily MMP-2 and MMP-9 in DR and also their participation in oxidative stress, mitochondrial dysfunction, and apoptosis, along with their involvement in various signaling pathways. This review also underscores different strategies to inhibit MMPs, thus suggesting that MMPs may represent a putative therapeutic target in the treatment of DR.

scholarly journals High glucose and diabetes increase the release of [3H]-d-aspartate in retinal cell cultures and in rat retinas

2006 ◽  
Vol 48 (6-7) ◽  
pp. 453-458 ◽  
Author(s):  
Ana R. Santiago ◽  
Tiago S. Pereira ◽  
Manuel J. Garrido ◽  
Armando J. Cristóvão ◽  
Paulo F. Santos ◽  
...  
Keyword(s):  
Cell Cultures ◽  
High Glucose ◽  
Retinal Cell

Effects of carbamylcholine on chick embryo aggregate retina cell cultures

1988 ◽  
Vol 46 ◽  
pp. 350-351
Author(s):  
Glenn M. Cohen ◽  
Radharaman Ray
Keyword(s):  
Cell Cultures ◽  
Single Cells ◽  
Retinal Cell ◽  
Cell Aggregates ◽  
High Concentration ◽  
In Ovo ◽  
Sterile Culture ◽  
Retinal Tissue ◽  
Synaptic Junctions ◽  
And Control

Retinal,cell aggregates develop in culture in a pattern similar to the in ovo retina, forming neurites first and then synapses. In the present study, we continuously exposed chick retinal cell aggregates to a high concentration (1 mM) of carbamylcholine (carbachol), an acetylcholine (ACh) analog that resists hydrolysis by acetylcholinesterase (AChE). This situation is similar to organophosphorus anticholinesterase poisoning in which the ACh level is elevated at synaptic junctions due to inhibition of AChE, Our objective was to determine whether continuous carbachol exposure either damaged cholino- ceptive neurites, cell bodies, and synaptic elements of the aggregates or influenced (hastened or retarded) their development.The retinal tissue was isolated aseptically from 11 day embryonic White Leghorn chicks and then enzymatically (trypsin) and mechanically (trituration) dissociated into single cells. After washing the cells by repeated suspension and low (about 200 x G) centrifugation twice, aggregate cell cultures (about l0 cells/culture) were initiated in 1.5 ml medium (BME, GIBCO) in 35 mm sterile culture dishes and maintained as experimental (containing 10-3 M carbachol) and control specimens.

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