Abstract
Background. Nitric oxide (NO) plays a key pathophysiological role in the development of diabetic retinopathy (DR), as it determines the state of endothelial dysfunction and causes numerous damaging mechanisms. Aim: to determine the content of NO and endothelial NO-synthase (eNOS) in DR and the possibility of their use as diagnostic and prognostic markers of its progression. Materials and methods. 136 patients with type 2 diabetes mellitus were examined, who were divided into groups: 1st – with non-proliferative (NPDR, 60 eyes), 2nd – with preproliferative DR (PPDR; 42 eyes) and 3rd – with proliferative DR (PDR; 34 eyes). Patients were examined and treated for 2 years. The blood NO content was determined by a biochemical method using the end products of its metabolism (NOx) using Griess reagent. The blood eNOS content was determined by an enzyme-linked immunosorbent assay. The analysis of the results was carried out in the EZR v.1.54 package (Austria). Results. In patients with DR, an increase in the blood NOx content was found (1.3-1.4 times; p<0.001) compared to the control group without diabetes. The NOx content at different stages of DR did not differ (p>0.05). The blood eNOS content by stages of DR significantly and progressively decreased, in NPDR it was 1.5 times lower than the control level, in PPDR – 1.6 times and in PDR – 3.7 times (p<0.001). The content of eNOS in NPDR and PDR did not differ statistically significantly from each other (p>0.05), but was higher than that in patients with PDR (by 2.3-2.4 times; p<0.05). The NOx content was correlated with systolic (r=-0.632) and diastolic (r=-0.506) pressure, glycated hemoglobin (r=0.216;), cholesterol and lipoproteins levels. The eNOS content was correlated with fasting glycemia (r=-0.257), central retinal thickness (r=-0.401) and volume (r=-0.391), glycated hemoglobin (r=-0.683), cholesterol and lipoproteins levels. The NOx cut-off level for DR in type 2 diabetes was determined, which was 4.88 μmol/l (prognostic sensitivity – 89.7%, specificity – 100%). The cut-off level of eNOS for NPDR/PPDR was less than 300 pg/ml, for PDR – less than 104.5 pg/ml (prognostic accuracy – 90.1%). The risk of DR progression after 2 years was inversely related to the blood eNOS content (p<0.001; OR=0.16; 95% CI 0.08-0.31). Conclusion. Thus, it was established that an increase in the NOx blood content can be considered a biomarker of DR in type 2 diabetes, and the eNOS blood content is a biomarker of DR and its progression