Endothelial TWIST1 promotes pathological ocular angiogenesis

Area of Science:

• Ophthalmology
• Molecular Biology
• Angiogenesis Research

Background:

• Pathological neovascularization is a key factor in blinding vascular eye diseases.
• Identifying molecular differences between pathological and normal vessels is crucial for new treatments.
• Twist-related protein 1 (TWIST1) is known to play a role in tumor and pulmonary angiogenesis.

Purpose of the Study:

• To investigate the role of TWIST1 in pathological ocular angiogenesis in mouse models.
• To determine if TWIST1 is a potential therapeutic target for blinding vascular eye diseases.

Main Methods:

• Analyzed Twist1 expression in oxygen-induced retinopathy (OIR) mouse models.
• Evaluated pathological ocular angiogenesis in Tie2-driven conditional Twist1 knockout mice using OIR and laser-induced choroidal neovascularization models.
• Assessed the effects of TWIST1 on angiogenesis and endothelial cell function using aortic ring and choroidal explant sprouting assays, and human retinal microvascular endothelial cells with TWIST1 siRNA.

Main Results:

• TWIST1 was highly expressed in pathological neovessels in OIR retinas.
• Conditional Twist1 depletion significantly reduced pathological neovessels in OIR and choroidal neovascularization models, with smaller lesions and decreased vascular leakage.
• Loss of Twist1 impaired vascular sprouting and reduced VEGFR2 expression and endothelial cell proliferation.

Conclusions:

• TWIST1 is a novel regulator of pathological ocular angiogenesis.
• TWIST1 represents a potential molecular target for therapeutic strategies aimed at suppressing pathological neovascularization in vascular eye diseases.