CircPDE4B inhibits retinal pathological angiogenesis via promoting degradation of HIF-1α though targeting miR-181c

Area of Science:

• Ophthalmology
• Molecular Biology
• Genetics

Background:

• Retinopathy of prematurity is a leading cause of childhood blindness globally.
• Effective treatments are crucial for managing this condition.
• Understanding the molecular mechanisms underlying retinopathy of prematurity is essential for developing targeted therapies.

Purpose of the Study:

• To investigate the role of circPDE4B in retinopathy of prematurity.
• To elucidate the molecular pathway involving circPDE4B, miR-181c, VHL, and HIF-1α in regulating pathological angiogenesis.
• To evaluate circPDE4B as a potential therapeutic target for retinopathy of prematurity.

Main Methods:

• Quantitative real-time PCR (qRT-PCR) and Western blot to assess gene and protein expression.
• MTT assay to evaluate cell proliferation.
• Luciferase assay to measure luciferase activity.
• Inverted phase-contrast light microscopy for observing vascular tube formation.

Main Results:

• CircPDE4B was downregulated, while HIF-1α and VEGFA were upregulated in retinopathy of prematurity models.
• Increasing circPDE4B inhibited HIF-1α and VEGFA expression, repressed cell proliferation, and reduced pathological angiogenesis.
• CircPDE4B promoted VHL expression by binding to miR-181c, ultimately facilitating VHL-mediated ubiquitin degradation of HIF-1α.

Conclusions:

• CircPDE4B suppresses VEGFA expression and pathological angiogenesis by promoting VHL-mediated degradation of HIF-1α via miR-181c.
• CircPDE4B demonstrates potential as an effective therapeutic target for retinopathy of prematurity.