ArticleAmerican journal of physiology. Cell physiology2025
NADPH oxidase 1-PKCδ-dependent ZO-1 phosphorylation mediates IL-33-induced inner blood-retinal barrier disruption in proliferative retinopathies.
Article in American journal of physiology. Cell physiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Effects of the glucagon-like peptide-1 receptor agonist liraglutide on retinal endothelial function and oxidative stress during sepsis.Frontiers in pharmacology · 2026Article
- Nanoparticle-Mediated Lutein Delivery for Diabetic Retinopathy: From Blood-Retinal Barrier Crossing to Neurovascular Unit Protection.International journal of nanomedicine · 2026Review
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4 authors.
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Abstract
Proliferative retinopathies are associated with abnormal angiogenesis that can result in visual impairment or vision loss. The tight junction complex regulates blood-retinal barrier integrity; however, its role in proliferative retinopathies is still at an early stage. Here, we used human retinal microvascular endothelial cells (HRMVECs) and a mouse model of oxygen-induced retinopathy (OIR) to investigate the impact of interleukin-33 (IL-33) signaling on tight junction disintegration and pathological angiogenesis. Our experimental findings demonstrate that IL-33 induces zonula occludens-1 (ZO-1) serine/threonine phosphorylation and tight junction disruption in HRMVECs. In addition, mass spectroscopy analysis revealed that treating HRMVECs with IL-33 induces ZO-1 phosphorylation at the Thr861 residue. Furthermore, we observed that NOX1-PKCδ (protein kinase C-δ) signaling modulates IL-33-induced ZO-1 phosphorylation and tight junction integrity in HRMVECs. We also observed that IL-33 depletion significantly reduces OIR-induced NOX1-PKCδ-ZO-1 signaling and vascular leakage in the ischemic retina. We also observed that the NOX1-specific inhibitor, fluoflavine (ML-090), attenuated OIR-induced NADPH oxidase activity and pathological retinal neovascularization in the ischemic retina. Thus, we infer that IL-33-mediated NOX1-PKCδ-ZO-1 signaling regulates ischemia-induced retinal endothelial cell tight junction disruption and retinal neovascularization.
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