Pannexin-1 Inhibits Pathologic Neovascularization in Oxygen-Induced Retinopathy by Targeting the HIF-1α/VEGF Pathway...

Area of Science:

• Ophthalmology
• Vascular Biology
• Molecular Medicine

Background:

• Retinopathy of prematurity (ROP) is a leading cause of childhood blindness, driven by pathological retinal neovascularization.
• Current ROP treatments have significant risks, necessitating safer preventive strategies.
• Pannexin-1 (Panx1) is investigated for its role in ROP pathogenesis and potential as a therapeutic target.

Purpose of the Study:

• To investigate the role of Pannexin-1 (Panx1) in retinopathy of prematurity (ROP).
• To explore Panx1 as a therapeutic target for ROP by modulating the HIF-1α/VEGF pathway.

Main Methods:

• Human retinal microvascular endothelial cells (HRMECs) were used.
• Transcriptomic sequencing identified differentially expressed genes.
• Validation included rt-qPCR, Western blotting, and CCK-8 assays.
• Probenecid (PBC) was used to inhibit Panx1.

Main Results:

• Transcriptomic sequencing revealed significant upregulation of Panx1 in ROP.
• Hypoxia induced Panx1, HIF-1α, and VEGF overexpression, confirmed by rt-qPCR and Western blotting.
• PBC treatment inhibited hypoxia-induced Panx1, HIF-1α, and VEGF.
• Hypoxia impaired HRMEC proliferation, and PBC further suppressed this effect.

Conclusions:

• Panx1 inhibition via PBC suppresses the HIF-1α/VEGF signaling pathway.
• Panx1 inhibition reduces hypoxia-induced endothelial cell proliferation.
• Targeting Panx1 offers a novel preventive strategy for ROP.