ArticleProceedings of the National Academy of Sciences of the United States of America2018
Suppression of connexin 43 phosphorylation promotes astrocyte survival and vascular regeneration in proliferative retinopathy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 42 citations in OpenAlex.
- Bridging Hypoxia and Vision Loss: The Emerging Role of Connexins in Local and Systemic Eye Diseases.International journal of molecular sciences · 2026Review
- Nuclear translocation of Cx43 promotes to CRC progression and associates with β-catenin accumulation.Cancer biology & therapy · 2025Article
- Ginsenoside Rg1 alleviates chronic stress-induced depression in rats by targeting Cx43-YAP axis.Acta pharmacologica Sinica · 2025Article
- Targeting Connexin 43 in Retinal Astrocytes Promotes Neuronal Survival in Glaucomatous Injury.Glia · 2025Article
- Targeting Connexins Biology as Therapeutic Strategies Against Retinal Diseases.Advances in experimental medicine and biology · 2025Review
- The Phenotype Changes of Astrocyte During Different Ischemia Conditions.Brain sciences · 2024Article
- Ventral Root Boundary Cap Cells of Rat Spinal Cord Contain Connexin-43.Bulletin of experimental biology and medicine · 2024Article
- Agonism of β3-Adrenoceptors Inhibits Pathological Retinal Angiogenesis in the Model of Oxygen-Induced Retinopathy.Investigative ophthalmology & visual science · 2024Article
- O-GlcNAcylation Inhibition Upregulates Connexin43 Expression in the Endothelium to Protect the Tight Junction Barrier in Diabetic Retinopathy.Investigative ophthalmology & visual science · 2023Article
- Connexin 43 Phosphorylation: Implications in Multiple Diseases.Molecules (Basel, Switzerland) · 2023Review
- Connexins Biology in the Pathophysiology of Retinal Diseases.Advances in experimental medicine and biology · 2023Article
- Upregulation of retinal VEGF and connexin 43 in murine nonarteritic anterior ischemic optic neuropathy induced with 577 nm laser.Experimental eye research · 2022Article
- Connexin and Pannexin Large-Pore Channels in Microcirculation and Neurovascular Coupling Function.International journal of molecular sciences · 2022Review
- Myopia Alters the Structural Organization of the Retinal Vasculature, GFAP-Positive Glia, and Ganglion Cell Layer Thickness.International journal of molecular sciences · 2022Article
- Amphiphilic aminoglycosides: Modifications that revive old natural product antibiotics.Frontiers in microbiology · 2022Review
- Wnt Signaling in Inner Blood-Retinal Barrier Maintenance.International journal of molecular sciences · 2021Review
- Gap Junctional Coupling Between Retinal Astrocytes Exacerbates Neuronal Damage in Ischemia-Reperfusion Injury.Investigative ophthalmology & visual science · 2021Article
- The role of gap junctions in cell death and neuromodulation in the retina.Neural regeneration research · 2021Review
- Short chain fatty acids inhibit endotoxin-induced uveitis and inflammatory responses of retinal astrocytes.Experimental eye research · 2021Article
- Connexin 43 phosphorylation by casein kinase 1 is essential for the cardioprotection by ischemic preconditioning.Basic research in cardiology · 2021Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Degeneration of retinal astrocytes precedes hypoxia-driven pathologic neovascularization and vascular leakage in ischemic retinopathies. However, the molecular events that underlie astrocyte loss remain unclear. Astrocytes abundantly express connexin 43 (Cx43), a transmembrane protein that forms gap junction (GJ) channels and hemichannels. Cx channels can transfer toxic signals from dying cells to healthy neighbors under pathologic conditions. Here we show that Cx43 plays a critical role in astrocyte apoptosis and the resulting preretinal neovascularization in a mouse model of oxygen-induced retinopathy. Opening of Cx43 hemichannels was not observed following hypoxia. In contrast, GJ coupling between astrocytes increased, which could lead to amplification of injury. Accordingly, conditional deletion of Cx43 maintained a higher density of astrocytes in the hypoxic retina. We also identify a role for Cx43 phosphorylation in mediating these processes. Increased coupling in response to hypoxia is due to phosphorylation of Cx43 by casein kinase 1δ (CK1δ). Suppression of this phosphorylation using an inhibitor of CK1δ or in site-specific phosphorylation-deficient mice similarly protected astrocytes from hypoxic damage. Rescue of astrocytes led to restoration of a functional retinal vasculature and lowered the hypoxic burden, thereby curtailing neovascularization and neuroretinal dysfunction. We also find that absence of astrocytic Cx43 does not affect developmental angiogenesis or neuronal function in normoxic retinas. Our in vivo work directly links phosphorylation of Cx43 to astrocytic coupling and apoptosis and ultimately to vascular regeneration in retinal ischemia. This study reveals that targeting Cx43 phosphorylation in astrocytes is a potential direction for the treatment of proliferative retinopathies.
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Registered trials
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