Spontaneous Neutrophil Extracellular Traps Release Are Inflammatory Markers Associated with Hyperglycemia and Renal Failure on Diabetic Retinopathy

Abstract

Diabetic retinopathy (DR) is the major microvascular complication of diabetes and causes vitreous traction and intraretinal hemorrhages leading to retinal detachment and total blindness. The evolution of diabetes is related to exacerbating inflammation caused by hyperglycemia and activation of inflammatory cells. Neutrophils are cells able to release structures of extracellular DNA and proteolytic enzymes called extracellular traps (NETs), which are associated with the persistence of inflammation in chronic pathologies. The purpose of the study was to determine the usefulness of neutrophil traps as indicators of DR progression in patients with type 2 diabetes (T2DM). We performed a case–control study of seventy-four cases classified into five groups (non-proliferative DR, mild, moderate, severe, and proliferative) and fifteen healthy controls. We found correlations between NETs and a diagnostic time of T2DM (r = 0.42; p < 0.0001), fasting glucose (r = 0.29; p < 0.01), glycated hemoglobin (HbA1c) (r = 0.31; p < 0.01), estimated glomerular filtration rate (eGFR) (r = −0.29; p < 0.01), and plasma osmolarity (r = 0.25; p < 0.01). These results suggest that due to NETs being associated with clinical indicators, such as HbA1c and eGFR, and that NETs are also associated with DR, clinical indicators might be explained in part through an NET-mediated inflammation process.

Cellular communication network factor 1 promotes retinal leakage in diabetic retinopathy via inducing neutrophil stasis and neutrophil extracellular traps extrusion

“…Importantly, we did not exclude patients with these complications in the DM group, potentially contributing to the higher levels of circulating NE. Moreover, our findings reveal a positive correlation between circulating NE and diabetes duration, FBG, and HbA1c, in line with previous research [ 62 ]. Given the associations of circulating NE with multiple clinical indicators and its link to various diabetic complications, the absence of a difference in NE levels between the DR and DM groups may, at least in part, be attributed to these confounding factors.…”

“…This newfound insight further substantiates the role of CCN1 in promoting retinal leakage, shedding light on its multifaceted impact on DR progression. Additionally, a multitude of studies have consistently demonstrated the elevation of circulating NETs markers in DR patients when compared to diabetic patients without DR [ 8 , 62 , 63 ]. Among these markers, circulating NE has been identified as an independent risk factor of DR [ 7 ].…”

Unveiling the Web: Exploring the Multifaceted Role of Neutrophil Extracellular Traps in Ocular Health and Disease

“…Song et al confirmed that elevated blood glucose increases the levels of DNA-histone complexes and activates factor XII, which increases the risk of DR [92]. The presence of NETs is also significantly associated with DR compared with non-DR patients [93]. Additionally, NETs have recently been associated with elevated levels of glucose and glycated hemoglobin and a poor estimated glomerular filtration rate, indicating its potential in monitoring and, potentially, predicting diabetes progression [93].…”

The Standard-Dose Heparin-Warfarin Remedy Partially Resolves Thrombi in the Right Superior Pulmonary Vein and Left Atrium and Ameliorates Type 2 Diabetes Mellitus

“…Moreover, PVTs can emit smaller particles, including neutrophil extracellular traps (NETs), and other components, such as DNA and histones. Currently, NETs are known to be associated with several diseases, such as type 2 diabetes mellitus (T2DM) [11,12], atherosclerosis, diabetic nephropathy [13], diabetic retinopathy [14] and gestational diabetes mellitus [15].…”