scholarly journals Secretogranin III as a disease-associated ligand for antiangiogenic therapy of diabetic retinopathy

2017 ◽  
Vol 214 (4) ◽  
pp. 1029-1047 ◽  
Author(s):  
Michelle E. LeBlanc ◽  
Weiwen Wang ◽  
Xiuping Chen ◽  
Nora B. Caberoy ◽  
Feiye Guo ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Neutralizing Antibodies ◽  
Vision Loss ◽  
New Technology ◽  
Antiangiogenic Therapy ◽  
Vascular Leakage ◽  
Oxygen Induced Retinopathy ◽  
Promising Target ◽  
And Control ◽  
Endothelial Growth Factor

Diabetic retinopathy (DR) is a leading cause of vision loss with retinal vascular leakage and/or neovascularization. Current antiangiogenic therapy against vascular endothelial growth factor (VEGF) has limited efficacy. In this study, we applied a new technology of comparative ligandomics to diabetic and control mice for the differential mapping of disease-related endothelial ligands. Secretogranin III (Scg3) was discovered as a novel disease-associated ligand with selective binding and angiogenic activity in diabetic but not healthy vessels. In contrast, VEGF bound to and induced angiogenesis in both diabetic and normal vasculature. Scg3 and VEGF signal through distinct receptor pathways. Importantly, Scg3-neutralizing antibodies alleviated retinal vascular leakage in diabetic mice with high efficacy. Furthermore, anti-Scg3 prevented retinal neovascularization in oxygen-induced retinopathy mice, a surrogate model for retinopathy of prematurity (ROP). ROP is the most common cause of vision impairment in children, with no approved drug therapy. These results suggest that Scg3 is a promising target for novel antiangiogenic therapy of DR and ROP.

MicroRNA-34a attenuates VEGF-mediated retinal angiogenesis via targeting Notch1

2019 ◽  
Vol 97 (4) ◽  
pp. 423-430 ◽  
Author(s):  
Shaoyang Shi ◽  
Yong Jin ◽  
Haishan Song ◽  
Xiaolong Chen
Keyword(s):  
Vision Loss ◽  
Tube Formation ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Matrix Metalloproteinase 2 ◽  
Luciferase Reporter ◽  
Luciferase Reporter Gene ◽  
Oxygen Induced Retinopathy ◽  
Gene Assay ◽  
Retinal Angiogenesis ◽  
Endothelial Growth Factor

Pathological angiogenesis in the retina is one of the main ocular diseases closely associated with vision loss. This work investigated the roles of microRNA-34a (miR-34a) and its potential target Notch1, in retinal angiogenesis. For this we used oxygen-induced retinopathy (OIR) rats and human retinal microvascular endothelial cells (HRMECs) stimulated with vascular endothelial growth factor (VEGF). We performed hematoxylin–eosin staining, Western blot for VEGF, and immunofluorescence staining for CD31 to verify the establishment of our OIR model. We observed down-regulation of miR-34a, and up-regulation of Notch1 and Hey1 in retinas from OIR rats. We found similar results with the VEGF-stimulated HRMECs. By performing MTT assay, cell scratch assay, tube formation assay, and by detecting the expression of matrix-metalloproteinase-2 (MMP-2), MMP-9, tissue inhibitors of metalloproteinases-1 (TIMP-1), and TIMP-2, we found that transfection of miR-34a ameliorated VEGF-mediated angiogenesis of HRMECs. We further observed that siRNA-induced gene silencing of Notch1 prevented VEGF-induced angiogenesis via regulating cell proliferation, cell migration, and tube formation of HRMECs. Additionally, activation of Notch1 by transfection of Notch1 plasmid attenuated the inhibitory effects of miR-34a on tube formation, in the present of VEGF. Results from our dual-luciferase reporter gene assay suggested that miR-34a targets Notch1. In summary, our data demonstrate that miR-34a attenuates retinal angiogenesis via targeting Notch1.

Combination Approaches Targeting Neurodegeneration, Oxidative stress and Inflammation in the Treatment of Diabetic Retinopathy

2021 ◽  
Vol 22 ◽  
Author(s):  
Siddhi Dilip Chalke ◽  
Pravin Popatrao Kale
Keyword(s):  
Oxidative Stress ◽  
Diabetic Retinopathy ◽  
Vision Loss ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Early Stages ◽  
Advanced Stages ◽  
Severe Vision Loss ◽  
Angiopoietin 2 ◽  
Endothelial Growth Factor

: Diabetic Retinopathy (DR) is one of the most severe ocular problems of diabetes. It is a microvascular complication that impairs the vision of diabetic individuals and can cause acquired blindness. Currently available treatment options like laser therapy, vitrectomy, intravitreal anti-vascular endothelial growth factor (VEGF) agents, and glucocorticoids help to reduce vision loss at advanced stages. In spite of the available therapies, patients with severe vision loss face difficulty in achieving normal vision. There is a need for development of newer treatment strategies to address the condition from the early stages. Multiple factors owing to complex pathophysiological events are responsible for this long-term complication. Neurodegeneration, inflammation, and oxidative stress are the three important factors associated with the development of DR. Oxidative stress is a major contributor to the onset and progression of DR. Pathological events like retinal neurodegeneration and inflammation damage the retina right in the early stages of DR. Different combinations of treatments targeting these pathological events are discussed in the present review. The first combination discussed is citicoline and resveratrol. The second combination is duloxetine and N-acetyl cysteine (NAC). These combinations may help in the early stages of DR. CD5-2 and angiopoietin-2 inhibitors is the third combination. This combination may help to manage diabetic macular edema. The main purpose of this article is to discuss the link between these pathologies and the three combination approaches with the objective of consideration of newer therapeutic approaches in research related to DR treatment.

scholarly journals The CURRENT TRENDS AND TREATMENTS IN DIABETIC RETINOPATHY

2019 ◽  
pp. 27-33
Author(s):  
FIROZ MV ◽  
VISHAL GUPTA N ◽  
SANDEEP KANNA
Keyword(s):  
Diabetic Retinopathy ◽  
Laser Photocoagulation ◽  
Vision Loss ◽  
Renin Angiotensin System ◽  
Chemical Degradation ◽  
Common Causes ◽  
The World ◽  
Different Types ◽  
New Treatment ◽  
Endothelial Growth Factor

The drastically increasing issues of the disease scenario currently are with different types of diabetes all over the world. It has been reported, approximately 592 million are suffering from the disease throughout the world. It affects differently in different patients with the disease. There have been reports that it is affected differently and also has different side effects. It is also been reported that diabetes mellitus leads to the cause of diabetic retinopathy (DR) and also diabetic macular edema. It is considered as one of the most common causes which is linked to DR. DR has been considered as one of the most important causes for the loss of vision or impaired vision. The drugs show different types of incompatibility such as toxicity, solubility issues, aggregation, and chemical degradation these can be improved by applying several methods. DR is classified according to “Airlie House” into different categories and based on different strategies and consideration. It was found that DR is the main cause for vision loss and also there no much strategies for development of new treatment. The treatment involved is laser photocoagulation and vitrectomy, among these the effective treatment, was found to be laser photocoagulation. This is mainly characterized as proliferative and non-proliferative DR. Different therapeutic agents have been taken for the study these includes vascular endothelial growth factor, renin-angiotensin system inhibitors and nonsteroidal anti-inflammatory drugs, they are certainly different interventions for the treatment, they are nanotechnology and liposome. Nanotechnology applied is the most effective and also acceptable way of treatment.

scholarly journals THE ROLE OF DYSLIPIDEMIA IN THE PROGRESSION OF DIABETIC RETINOPATHY

2017 ◽  
pp. 44-46
Author(s):  
A. G. Kuzmin ◽  
S. A. Martynov ◽  
M. V. Shestakova
Keyword(s):  
Diabetic Retinopathy ◽  
Growth Factor ◽  
Large Scale ◽  
Vision Loss ◽  
Systemic Blood Pressure ◽  
Leading Role ◽  
Retinal Blood Vessels ◽  
Risk Of Progression ◽  
Angiopoietin 2 ◽  
Endothelial Growth Factor

Angiogenesis factors, growth factors (vascular endothelial growth factor (VEGF), angiopoietin-2, insulin-like growth factor, etc.) and cytokines play the leading role in the production by endothelial cells of new retinal blood vessels, increased vascular permeability resulting in exudation and macular edema leading to the development of irreversible complications and vision loss. Although large-scale clinical trials demonstrated that tight control of glycemia and normalization of systemic blood pressure reduce the risk of progression of diabetic retinopathy (DR), the relationship between lipid disorders and retinal damage is not fully understood.

scholarly journals Blockade of Vascular Endothelial Growth Factor Receptor 1 Prevents Inflammation and Vascular Leakage in Diabetic Retinopathy

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Jianbo He ◽  
Hong Wang ◽  
Ying Liu ◽  
Wen Li ◽  
Dorothy Kim ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Diabetic Retinopathy ◽  
Growth Factor ◽  
Growth Factor Receptor ◽  
Vascular Leakage ◽  
Intercellular Adhesion Molecule ◽  
Vascular Endothelial ◽  
Western Blots ◽  
Junction Protein ◽  
Endothelial Growth Factor

Diabetic retinopathy (DR) is a leading cause of blindness in working age adults. The objective of this study is to investigate the effects of vascular endothelial growth factor receptor 1 (VEGFR1) blockade on the complications of DR. Experimental models of diabetes were induced with streptozotocin (STZ) treatment or Insulin2 gene mutation (Akita) in mice. Protein expression and localization were examined by western blots (WB) and immunofluorescence (IF). mRNA expression was quantified by PCR array and real-time PCR. The activity of VEGFR1 signaling was blocked by a neutralizing antibody called MF1. Vascular leakage was evaluated by measuring the leakage of [3H]-mannitol tracer into the retina and the IF staining of albumin. VEGFR1 blockade significantly inhibited diabetes-related vascular leakage, leukocytes-endothelial cell (EC) adhesion (or retinal leukostasis), expression of intercellular adhesion molecule- (ICAM-) 1 protein, abnormal localization and degeneration of the tight junction protein zonula occludens- (ZO-) 1, and the cell adhesion protein vascular endothelial (VE) cadherin. In addition, VEGFR1 blockade interfered with the gene expression of 10 new cytokines and chemokines: cxcl10, il10, ccl8, il1f6, cxcl15, ccl4, il13, ccl6, casp1, and ccr5. These results suggest that VEGFR1 mediates complications of DR and targeting this signaling pathway represents a potential therapeutic strategy for the prevention and treatment of DR.

scholarly journals Neuroprotection as a Therapeutic Target for Diabetic Retinopathy

2016 ◽  
Vol 2016 ◽  
pp. 1-18 ◽  
Author(s):  
Cristina Hernández ◽  
Massimo Dal Monte ◽  
Rafael Simó ◽  
Giovanni Casini
Keyword(s):  
Clinical Trials ◽  
Diabetic Retinopathy ◽  
Animal Studies ◽  
Vision Loss ◽  
Vascular Lesions ◽  
Vascular Endothelial ◽  
Neuroprotective Strategies ◽  
Current Therapies ◽  
Retinal Neurodegeneration ◽  
Endothelial Growth Factor

Diabetic retinopathy (DR) is a multifactorial progressive disease of the retina and a leading cause of vision loss. DR has long been regarded as a vascular disorder, although neuronal death and visual impairment appear before vascular lesions, suggesting an important role played by neurodegeneration in DR and the appropriateness of neuroprotective strategies. Upregulation of vascular endothelial growth factor (VEGF), the main target of current therapies, is likely to be one of the first responses to retinal hyperglycemic stress and VEGF may represent an important survival factor in early phases of DR. Of central importance for clinical trials is the detection of retinal neurodegeneration in the clinical setting, and spectral domain optical coherence tomography seems the most indicated technique. Many substances have been tested in animal studies for their neuroprotective properties and for possible use in humans. Perhaps, the most intriguing perspective is the use of endogenous neuroprotective substances or nutraceuticals. Together, the data point to the central role of neurodegeneration in the pathogenesis of DR and indicate neuroprotection as an effective strategy for treating this disease. However, clinical trials to determine not only the effectiveness and safety but also the compliance of a noninvasive route of drug administration are needed.

scholarly journals Bevacizumab and Treatment Regimes in Diabetic Retinopathy and Diabetic Macular Edema

2018 ◽  
pp. 155-159
Keyword(s):  
Diabetic Retinopathy ◽  
Macular Edema ◽  
Diabetic Macular Edema ◽  
Proliferative Diabetic Retinopathy ◽  
Vision Loss ◽  
Intravitreal Bevacizumab ◽  
Retinal Neovascularization ◽  
Diabetic Patients ◽  
Treatment Regimes ◽  
Endothelial Growth Factor

Diabetic macular edema and proliferative diabetic retinopathy is the most important cause of vision loss in diabetic patients. Vascular endothelial growth factor has been shown to play a major role in retinal neovascularization and vascular hyperpermeability in eyes with diabetic patients. Recent studies have demonstrated the usefulness of an intravitreal injection of bevacizumab in the reduction of diabetic macular edema, vascular permeability, and fibrovascular proliferation in retinal neovascularization secondary to proliferative diabetic retinopathy. This review aimed to evaluate the intravitreal bevacizumab in diabetic retinopathy and diabetic macular edema.

scholarly journals Neuroprotective factors of the retina and their role in promoting survival of retinal ganglion cells: a review

2021 ◽  
Author(s):  
Ewa Fudalej ◽  
Magdalena Justyniarska ◽  
Kaja Kasarełło ◽  
Jacek Dziedziak ◽  
Jacek P Szaflik ◽  
...  
Keyword(s):  
Growth Factor ◽  
Retinal Ganglion Cells ◽  
Neurotrophic Factor ◽  
Vision Loss ◽  
Ganglion Cells ◽  
Pigment Epithelium ◽  
Vascular Endothelial ◽  
Retinal Ganglion ◽  
Oxygen Induced Retinopathy ◽  
Endothelial Growth Factor

Retinal ganglion cells (RGC) play a crucial role in the visual pathway. As their axons form the optic nerve, apoptosis of these cells causes neurodegenerative vision loss. RGC death could be triggered by increased intraocular pressure, advanced glycation end products, or mitochondrial dysfunction. In this review, we summarize the role of some neuroprotective factors in RGC injury: ciliary neurotrophic factor (CNTF), nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), pigment epithelium-derived factor (PEDF), glial cell line-derived neurotrophic factor (GDNF), and Norrin. Each, in their own unique way, prevents RGC damage caused by glaucoma, ocular hypertension, ischemic neuropathy, and even oxygen-induced retinopathy. These factors are produced mainly by neurons, leukocytes, glial cells, and epithelial cells. Neuroprotective factors act via various signaling pathways, including JAK/STAT, MAPK, TrkA, and TrkB, which promotes RGC survival. Many attempts have been made to develop therapeutic strategies using these factors. There are ongoing clinical trials with CNTF and NGF, but they have not yet been accepted for clinical use.

Gut microbiome a promising target for management of respiratory diseases

2020 ◽  
Vol 477 (14) ◽  
pp. 2679-2696
Author(s):  
Riddhi Trivedi ◽  
Kalyani Barve
Keyword(s):  
Respiratory Diseases ◽  
New Technology ◽  
Bacterial Flora ◽  
Systemic Circulation ◽  
The Body ◽  
Lung Pathology ◽  
Promising Target ◽  
Current Therapies ◽  
Intestinal Microbial Flora ◽  
On Chip

The intestinal microbial flora has risen to be one of the important etiological factors in the development of diseases like colorectal cancer, obesity, diabetes, inflammatory bowel disease, anxiety and Parkinson's. The emergence of the association between bacterial flora and lungs led to the discovery of the gut–lung axis. Dysbiosis of several species of colonic bacteria such as Firmicutes and Bacteroidetes and transfer of these bacteria from gut to lungs via lymphatic and systemic circulation are associated with several respiratory diseases such as lung cancer, asthma, tuberculosis, cystic fibrosis, etc. Current therapies for dysbiosis include use of probiotics, prebiotics and synbiotics to restore the balance between various species of beneficial bacteria. Various approaches like nanotechnology and microencapsulation have been explored to increase the permeability and viability of probiotics in the body. The need of the day is comprehensive study of mechanisms behind dysbiosis, translocation of microbiota from gut to lung through various channels and new technology for evaluating treatment to correct this dysbiosis which in turn can be used to manage various respiratory diseases. Microfluidics and organ on chip model are emerging technologies that can satisfy these needs. This review gives an overview of colonic commensals in lung pathology and novel systems that help in alleviating symptoms of lung diseases. We have also hypothesized new models to help in understanding bacterial pathways involved in the gut–lung axis as well as act as a futuristic approach in finding treatment of respiratory diseases caused by dysbiosis.

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