Diabetic retinopathy and endothelin system: microangiopathy versus endothelial dysfunction

Abstract

In the face of the global epidemic of diabetes, it is critical that we update our knowledge about the pathogenesis of diabetes and the related micro alterations on the vascular network in the body. This may ultimately lead to early diagnosis and novel treatment options for delaying the progression of diabetic complications. Research has recently revealed the pivotal role of endothelin in the pathogenesis of diabetic complications, particularly in the regulation of the capillary flow, which is affected in the course of retinopathy. Although there are several reviews on various approaches to the treatment of diabetes, including normalization of glucose and fat metabolism, no reviews in literature have focused on the endothelin system as a therapeutic target or early indicator of diabetic microangiopathy. In this review, we summarize some of the experimental and clinical evidence suggesting that current therapeutic approaches to diabetes may include the modulation of the blood concentration of compounds of the endothelin system. In addition, we will briefly discuss the beneficial effects produced by the inhibition of the production of high levels of endothelin in vasculopathy, with focus on diabetic retinopathy. The cutting-edge technology currently widely used in opththalmology, such as the OCT angiography, allows us to detect very early retinal morphological changes alongside alterations in choroidal and retinal vascular network. Combination of such changes with highly sensitive measurements of alterations in serum concentrations of endothelin may lead to more efficient early detection and treatment of diabetes and related macro/microvascular complications.

Short- and long-term impact of hyperoxia on the blood and retinal cells’ transcriptome in a mouse model of oxygen-induced retinopathy

“…14 Edn2 gene, which showed 18.6-fold increased expression on P17, encodes endothelin (ET) 2, a potent vasoconstrictor that contributes to regulation of the retinal blood flow, and may exert mitogenic, pro-oxidative, and proinflammatory effects. 15 Our results of Edn2 overexpression confirmed previously published findings of increased abundance of Edn2 transcripts in various retinal injuries. 16 A pharmacological blockade of the ET system prevented pathological neovascularization in a murine model of OIR.…”

miR-874 ameliorates retinopathy in diabetic rats by NF-κB signaling pathway

“…miRNAs can interact with the 3'UTR region of the mRNA for a specific target gene by sequence-specific mode to regulate the protein expression of target gene. Recent studies have revealed that miRNAs participate in the development and progression of DR and are involved in multiple pathogenesis of DR [14][15][16]. We found a site where miR-874 bound to the NF-κB p65 by the prediction on a bioinformatics website, and the down-regulation of miR-874 expression in rats with myocardial ischemia reperfusion injury exerted an inhibitory effect on inflammation and injury [17,18].…”

miR-874 ameliorates retinopathy in diabetic rats by NF-κB signaling pathway

“…miRNAs can regulate the protein expression a speci c target gene by interacting with the 3'UTR region of its mRNA via sequence-speci c mode. Recent studies have revealed that miRNAs participate in the development and progression of DR and are involved in multiple pathogenesis of DR [14][15][16]. We found a site where miR-874 bound to the NF-κB p65 by the bioinformatics website, and the down-regulation of miR-874 expression in rats with myocardial ischemia reperfusion injury exerted an inhibitory effect on in ammation and injury [17,18].…”