scholarly journals Validation of biomarkers of diabetic retinopathy for preventing and predictive medicine in diabetic complications

2014 ◽  
Vol 5 (S1) ◽  
Author(s):  
Folami Lamoke ◽  
Sean Shaw ◽  
Babak Baban ◽  
Anna Lisa Montemari ◽  
Francesco Facchiano ◽  
...  
Author(s):  
Rujman Khan ◽  
Xin Yee Ooi ◽  
Matthew Parvus ◽  
Laura Valdez ◽  
Andrew Tsin

Hyperglycemic conditions and disruptions to glucose-regulating pathways lead to increased formation of highly reactive aldehydes, methylglyoxal and glyoxal, which react with certain arginine and lysine residues in proteins to form advanced glycation end products (AGEs). These AGEs damage the integrity of the retinal vasculature predominantly through two mechanisms: non-receptor-mediated damage, which pertains to the interaction with extracellular matrix and its functional properties, and receptor-mediated damage through AGE interactions with their receptors (RAGE) on pericytes and Muller cells. Damage occurring between AGE and RAGE potentially generates reactive oxygen species, inflammatory cytokines, and growth factors. Both mechanisms result in increased permeability of endothelial tight junctions, and this increased permeability can lead to leaking and eventually ischemia. Once this ischemia becomes significant, neovascularization can occur, the hallmark of proliferative diabetic retinopathy. Current pharmaceutical studies have shown the potential of AGE inhibitors, such as aminoguanidine, in decreasing AGE production, thus minimizing its effects in hyperglycemic conditions. Other pharmaceutical interventions, such as Tanshinone IIA, aim to protect cells from the impacts of AGEs. Future research will not only continue to understand the properties of AGEs and their effects on diabetes and diabetic complications like diabetic retinopathy but will also explore how they impact other diseases.


2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Daniel Gologorsky ◽  
Aristomenis Thanos ◽  
Demetrios Vavvas

The global prevalence of diabetes is estimated to be 336 million people, with diabetic complications contributing to significant worldwide morbidity and mortality. Diabetic retinopathy results from cumulative microvascular damage to the retina and inflammation is recognized as a critical driver of this disease process. This paper outlines the pathophysiology leading to proliferative diabetic retinopathy and highlights many of the inflammatory, angiogenic, and cytokine mediators implicated in the development and progression of this disease. We focus a detailed discussion on the current targeted therapeutic interventions used to treat diabetic retinopathy.


2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Haoran Li ◽  
Biao Li ◽  
Yanlin Zheng

Aim of the Study. To study the mechanism of Compound-Xueshuantong Capsule in diabetic retinopathy treatment based on network pharmacology. Materials and Methods. The components with oral bioavailability ≥30% and drug similarity ≥0.18 were screened by the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP), and the effective grouping of Compound-Xueshuantong Capsule was obtained. At the same time, the targets of each drug active component in the Compound-Xueshuantong Capsule were obtained by searching the TCMSP. The effective components and targets of the Compound-Xueshuantong Capsule were annotated by the UniProt database, and the disease treatment targets were searched by the GeneCards database. The disease treatment target is intersected with the drug target and the Wayne diagram is drawn by VennDiagram. The active ingredient targets of the intersection and Compound-Xueshuantong Capsule were inputted into Cytoscape 3.7.2 software to construct the active ingredient-target-disease interaction network. The above targets were inputted into the String database for protein-protein interaction network prediction. Finally, by using the DAVID database, GO and KEGG enrichment analysis was carried out to reveal the potential signal pathway of the Compound-Xueshuantong Capsule in diabetic retinopathy treatment. Results. 93 active components of the Compound-Xueshuantong Capsule and 92 targets for treating diabetic retinopathy were screened. The main active components of the Compound-Xueshuantong Capsule in treating diabetic retinopathy were quercetin, luteolin, kaempferol, beta-sitosterol, isorhamnetin, and tanshinone IIa. The effect of the Compound-Xueshuantong Capsule on diabetic retinopathy may be related to IL6, EFGR, CASP3, and VEGFA. In addition, the treatment of diabetic retinopathy mainly involves in the regulation of nuclear receptors and transcription factors in vivo. The target of the Compound-Xueshuantong Capsule in diabetic retinopathy treatment is significantly enriched in the AGE-RAGE signal pathway, TNF signal pathway, HIF-1 signal pathway, and VEGF signal pathway in diabetic complications. Conclusion. Compound-Xueshuantong Capsule can treat diabetic retinopathy through multitarget, multipathway, and multipathway regulation of the biomolecular network. The potential biological mechanism of the Compound-Xueshuantong Capsule in diabetic retinopathy treatment may be related to the AGE-RAGE signal pathway, TNF signal pathway, HIF-1 signal pathway, and VEGF signal pathway in diabetic complications, but these findings still need to be confirmed by further clinical research.


2020 ◽  
Vol 16 ◽  
Author(s):  
Dipayan Roy ◽  
Anupama Modi ◽  
Manoj Khokar ◽  
Shrimajunath Sankanagoudar ◽  
Dharamveer Yadav ◽  
...  

Background: Diabetes Mellitus is a multifactorial disease encompassing various pathogenic pathways. To avoid morbidity and mortality related to diabetic complications, early detection of disease complications as well as targeted therapeutic strategies, are essential. Introduction: MicroRNAs (miRs) are short non-coding RNA molecules that regulate eukaryotic post-transcriptional gene expression. MicroRNA-21 has diverse gene regulatory functions and plays a significant role in various complications of Type 2 diabetes mellitus (T2DM). Methods: The study included electronic database searches on Pubmed, Embase, and Web of Science with the search items MicroRNA21 and each of the diabetic complications. The search was carried out up to November, 2019. Result: MicroRNA-21 modulates diabetic cardiomyopathy by affecting vascular smooth muscle cell proliferation and apoptosis, cardiac cell growth and death, and cardiac fibroblast functions. At the renal tubules, miR-21 can regulate the mesangial expansion, interstitial fibrosis, macrophage infiltration, podocyte loss, albuminuria and fibrotic and inflammatory gene expression related to diabetic nephropathy. Overexpression of miR-21 has been seen to play a pivotal role in the pathogenesis of diabetic retinopathy by contributing to diabetes-induced endothelial dysfunction as well as the low-grade inflammation. Conclusion: Considering the raised levels of miR-21 in various diabetic complications, it may prove to be a candidate biomarker for diabetic complications. Further, miR-21 antagonists have shown great potential in the treatment of diabetic cardiomyopathy, diabetic nephropathy, diabetic retinopathy, and diabetic neuropathy related complications in the future. The current review is the first of its kind encompassing the roles miR-21 plays in various diabetic complications, with a critical discussion of its future potential role as a biomarker and therapeutic target.


2010 ◽  
Author(s):  
Samuel Dagogo-Jack

The long-term complications of diabetes mellitus include retinopathy, nephropathy, and neuropathy. Diabetic retinopathy can result in loss of vision; nephropathy may lead to end-stage kidney disease (ESKD); and neuropathy poses the risk of foot ulcers, amputation, Charcot joints, sexual dysfunction, and potentially disabling dysfunction of the stomach, bowel, and bladder. Hyperglycemia sufficient to cause pathologic and functional changes in target tissues may be present for some time before clinical symptoms lead to a diagnosis of diabetes, especially in patients with type 2 diabetes. Diabetic patients are also at increased risk for atherosclerotic cardiovascular, peripheral vascular, and cerebrovascular disease. These conditions may be related to hyperglycemia, as well as to the hypertension and abnormal lipoprotein profiles that are often found in diabetic patients. Prevention of these complications is a major goal of current therapeutic policy and recommendations for all but transient forms of diabetes. This chapter describes the pathogenesis, screening, prevention, and treatment of diabetic complications, as well as the management of hyperglycemia in the hospitalized patient. Figures illustrate the pathways that link high blood glucose levels to microvascular and macrovascular complications; fundus abnormalities in diabetic retinopathy; the natural history of nephropathy in type 1 diabetes; cumulative incidence of first cardiovascular events, stroke, or death from cardiovascular disease in patients with type 1 diabetes; the effect of intensive glycemic therapy on the risk of myocardial infarction, major cardiovascular event, or cardiovascular death in patients with type 2 diabetes; and risk of death in patients with type 2 diabetes who receive intensive therapy of multiple risk factors or conventional therapy. Tables describe screening schedules for diabetic complications in adults, foot care recommendations for patients with diabetes, and comparison of major trials of intensive glucose control. This chapter has 238 references.


2010 ◽  
Vol 2010 ◽  
pp. 1-12 ◽  
Author(s):  
Masayoshi Takeuchi ◽  
Jun-ichi Takino ◽  
Sho-ichi Yamagishi

Diabetic complications are a leading cause of acquired blindness, end-stage renal failure, and accelerated atherosclerosis, which are associated with the disabilities and high mortality rates seen in diabetic patients. Continuous hyperglycemia is involved in the pathogenesis of diabetic micro- and macrovascular complicationsviavarious metabolic pathways, and numerous hyperglycemia-induced metabolic and hemodynamic conditions exist, including increased generation of various types of advanced glycation end-products (AGEs). Recently, we demonstrated that glyceraldehyde-derived AGEs, the predominant structure of toxic AGEs (TAGE), play an important role in the pathogenesis of angiopathy in diabetic patients. Moreover, recent evidence suggests that the interaction of TAGE with the receptor for AGEs (RAGE) elicits oxidative stress generation in numerous types of cells, all of which may contribute to the pathological changes observed in diabetic complications. In this paper, we discuss the pathophysiological role of the TAGE-RAGE system in the development and progression of diabetic retinopathy.


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