Changes in the amount of matrix metalloproteinases and kynurenines in individuals with diabetic retinopathy, their role in the development of the disease

INTRODUCTION: Diabetic retinopathy (DR) is one of most common chronic complications of diabetes mellitus (DM). The pathogenesis of DR is complex and involves interaction of many molecular mechanisms, and far not all of them have been studied. AIM: To determine the level of matrix metalloproteinases and kynurenines in the blood of patients with type 2 DM (T2DM) with different stages of DR. MATERIALS AND METHODS: Four groups of patients were formed: Group 1 (control) — 21 healthy individuals; Group 2 — 21 patients with prediabetes, Group 3 — 21 patients with T2DM, Group 4 — 63 patients with T2DM and DR. Then patients with DR were divided into groups (n = 21): Group 5 — non-proliferative stage of DR, Group 6 — preproliferative DR, Group 7 — proliferative DR. In the blood serum, the following parameters were determined: the content of metalloproteinases (MMP) types 2 and 9 (MMP-2, MMP-9) by the enzyme immunoassay; in blood plasma — the concentration of kynurenines by the high-performance liquid chromatography. RESULTS: Significant differences were recorded in the studied parameters between healthy individuals and patients with diabetes. Subsequently, the results of patients with different stages of DR were compared with the data of patients with diabetes without vascular complications. In the preproliferative stage of DR, an excess of blood MMP-2 by 87.9% (p = 0.030) and MMP-9 by 37% (p = 0.049) was recorded relative to the individuals with diabetes. In the proliferative stage of DR, the levels of MMP-9 and MMP-2 were higher than those of not only the comparison group, but also the groups of non-proliferative and preproliferative stages of DR. In the preproliferative stage of DR, an increased concentration of 3-hydroxykynurenine was also recorded. The maximum increase in kynurenines was noted in the final stage of DR (p 0.05 relative to the groups of non-proliferative and preproliferative DR). CONCLUSIONS: In the analyzed groups of individuals, the concentrations of kynurenines increased as the underlying disease progressed. The level of MMP-9 was higher in diabetes mellitus, and in the proliferative stage of DR, the values of MMP-9 and MMP-2 increased.