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

Abstract

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.

Keywords: Chinese medicine; Qideng Mingmu Capsule; angiopoietin; oxygen-induced retinopathy; retinal neovascularization; tyrosine kinase receptor.