Qideng Mingmu Capsules Ameliorates Retinal Neovascularization by Regulating Ang/Tie2 Signaling Pathway.

OBJECTIVE

To investigate the inhibitory effects and underlying mechanisms of Qideng Mingmu Capsules (QD) on retinal neovascularization (RNV).

METHODS

Seven-day-old C57BL/6J mice were assigned to the following groups: control, oxygen-induced retinopathy (OIR), low-, medium-, high-dose QD (225, 450, and 900 mg/g daily), and angiopoietin 1 (Ang1), 20 mice in each group. Except for the control group, an OIR model was induced by exposing mice to a hyperoxic environment for 5 d (postnatal days 7-12), followed by a normoxic environment for 5 d (postnatal days 12-17). From day 12, the treatment groups received QD orally or Ang1 via binocular intravitreal injection. On day 17, hematoxylin and eosin staining and fluorescein isothiocyanate-dextran staining were performed to evaluate RNV growth. Immunofluorescence staining, immunohistochemistry, and Western blotting were used to analyze the expressions of Ang/tyrosine kinase with immunoglobulin and epidermal growth factor homology domain-2 (Tie2) signaling pathway, hypoxia-inducible factor-1α (HIF-1α), and retinal vascular maturation markers. In addition, the effects of QD on the viability of rat retinal microvascular endothelial cells (rRMECs) was assessed.

RESULTS

QD significantly inhibited RNV formation, reduced RNV density, increased the expressions of Ang1, Tie2, and phosphorylated protein kinase B, and decreased the expression of Ang2 (P<0.05 or P<0.01). QD also enhanced retinal vascular pericyte coverage, reduced HIF-1α expression, and increased vascular endothelial cadherin levels (P<0.05 or P<0.01). Furthermore, no adverse effects were observed on the viability of rRMECs after QD intervention.

CONCLUSIONS

QD effectively inhibited RNV formation, promoted neovascular maturation and remodeling, and protected retinal function by modulating the Ang/Tie2 signaling pathway. Therefore, QD may serve as a promising therapeutic option for retinal neovascular diseases.