Mechanism of circ-001209 on retinal angiogenesis in rats with diabetic retinopathy by regulating interleukin-33/suppression of tumorigenicity 2 signaling pathway

Objective To investigate the mechanism of circ-001209 on retinal angiogenesis in rats with diabetic retinopathy (DR) by regulating the interleukin-33/suppression of tumorigenicity 2 (IL-33/ST2) signaling pathway.

Methods Fifty rats were randomly divided into Col group, DR group, si-circ-NC group, si-circ-001209 group, and si-circ-001209+IL-33 group, with 10 rats in each group. The levels of fasting plasma glucose (FPG) and fasting insulin (FINS) in rats were detected; fundus fluorescein angiography (FFA) was used to detect retinal angiogenesis; the enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of angiogenesis-related factors and inflammatory factors in serum; the hematoxylin-eosin (HE) staining was used to detect histopathological changes in the retina; the periodic acid-Schiff (PAS) staining was used to detect the number of retinal microvascular formations; the Western blotting was used to detect the protein expression levels of IL-33, ST2, vascular endothelial growth factor (VEGF), hypoxia-inducible factor-1α (HIF-1α), and intercellular adhesion molecule-1 (ICAM-1) in retinal tissues.

Results Compared with the Col group, the DR group and si-circ-NC group showed significant increase in levels of FPG, FINS, serum VEGF, angiopoietin-1 (Ang-1), IL-6, IL-33, tumor necrosis factor-α (TNF-α), the number of microvascular formation, and the protein expression levels of IL-33, ST2, VEGF, HIF-1α, and ICAM-1 in retinal tissues (P < 0.05); the si-circ-001209 group showed significant decrease in levels of FPG, FINS, serum VEGF, Ang-1, IL-6, IL-33, TNF-α, the number of microvascular formation, and the protein expression levels of IL-33, ST2, VEGF, HIF-1α, and ICAM-1 in retinal tissues compared with the si-circ-NC group (P < 0.05); the si-circ-001209+IL-33 group showed significant increase in levels of FPG, FINS, serum VEGF, Ang-1, IL-6, IL-33, TNF-α, the number of microvascular formations, and the protein expression levels of IL-33, ST2, VEGF, HIF-1α, and ICAM-1 in retinal tissues compared with the si-circ-001209 group (P < 0.05).

Conclusions Knockdown of circ-001209 can inhibit retinal angiogenesis in rats with DR, potentially through inhibiting the activation of the IL-33/ST2 signaling pathway and reducing inflammation.