ArticleInvestigative ophthalmology & visual science2014
High glucose alters Cx43 expression and gap junction intercellular communication in retinal Müller cells: promotes Müller cell and pericyte apoptosis.
Article in Investigative ophthalmology & visual science, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 60 citations in OpenAlex.
- Elucidating programmed cell death in diabetic retinal microangionopathy and neurodegeneration: unraveling molecular mechanisms and therapeutic actions of natural products.Inflammopharmacology · 2025Review
- Brain Pericytes Enhance MFSD2A Expression and Plasma Membrane Localization in Brain Endothelial Cells Through the PDGF-BB/PDGFRβ Signaling Pathway.International journal of molecular sciences · 2025Article
- Impaired Communication through Gap Junctions Reduces the Angiogenic Potential of the Secretome in Mesenchymal Stromal Cell-Endothelial Cell Interactions In Vitro.Bulletin of experimental biology and medicine · 2024Article
- Microvascular destabilization and intricated network of the cytokines in diabetic retinopathy: from the perspective of cellular and molecular components.Cell & bioscience · 2024Review
- Protector Role of Cx30.2 in Pancreatic β-Cell against Glucotoxicity-Induced Apoptosis.Biology · 2024Article
- Oncostatin M Reduces Pathological Neovascularization in the Retina Through Müller Cell Activation.Investigative ophthalmology & visual science · 2024Article
- Single-Cell RNA Sequencing Reveals Transcriptional Signatures and Cell-Cell Communication in Diabetic Retinopathy.Endocrine, metabolic & immune disorders drug targets · 2024Article
- Diabetic Müller-Glial-Cell-Specific Il6ra Knockout Mice Exhibit Accelerated Retinal Functional Decline and Thinning of the Inner Nuclear Layer.Investigative ophthalmology & visual science · 2023Article
- Suppression of cAMP/PKA/CREB signaling ameliorates retinal injury in diabetic retinopathy.The Kaohsiung journal of medical sciences · 2023Article
- The Role of Müller Cells in Diabetic Macular Edema.Investigative ophthalmology & visual science · 2023Review
- Generation and characterization of a Müller-glial-cell-specific Il6ra knockout mouse to delineate the effects of IL-6 trans-signaling in the retina.Scientific reports · 2022Article
- Mechanisms of β-adrenergic receptors agonists in mediating pro and anti-apoptotic pathways in hyperglycemic Müller cells.Molecular biology reports · 2022Article
- Connexins and Glucose Metabolism in Cancer.International journal of molecular sciences · 2022Review
- The role of retinal Müller cells in diabetic retinopathy and related therapeutic advances.Frontiers in cell and developmental biology · 2022Review
- The protective effect of pericytes on vascular permeability after hemorrhagic shock and their relationship with Cx43.Frontiers in physiology · 2022Article
- Redox and Calcium Alterations of a Müller Cell Line Exposed to Diabetic Retinopathy-Like Environment.Frontiers in cellular neuroscience · 2022Article
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- 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
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
purposeTo investigate whether high glucose (HG) alters connexin 43 (Cx43) expression and gap junction intercellular communication (GJIC) activity in retinal Müller cells, and promotes Müller cell and pericyte loss.
methodsRetinal Müller cells (rMC-1) and cocultures of rMC-1 and retinal pericytes were grown in normal (N) or HG (30 mM glucose) medium. Additionally, rMC-1 transfected with Cx43 small interfering RNA (siRNA) were grown as cocultures with pericytes, and rMC-1 transfected with Cx43 plasmid were grown in HG. Expression of Cx43 was determined by Western blotting and immunostaining and GJIC was assessed by scrape-loading dye transfer (SLDT) technique. Apoptosis was analyzed by TUNEL or differential staining assay, and Akt activation by assessing Akt phosphorylation.
resultsIn monocultures of rMC-1 and cocultures of rMC-1 and pericytes, Cx43 protein level, number of Cx43 plaques, GJIC, and Akt phosphorylation were significantly reduced in HG medium. Number of TUNEL-positive cells was also significantly increased in rMC-1 monocultures and in rMC-1 and pericyte cocultures grown in HG medium. Importantly, when rMC-1 transfected with Cx43 siRNA were grown as cocultures with pericytes, a significant decrease in GJIC, and increase in TUNEL-positive cells was observed, concomitant with decreased Akt phosphorylation. Upregulation of Cx43 rescued rMC-1 from HG-induced apoptosis.
conclusionsGap junction communication between Müller cells and pericytes is essential for their survival. Downregulation of Cx43 that is HG induced and impairment of GJIC activity in Müller cells contributes to loss of glial and vascular cells associated with the pathogenesis of diabetic retinopathy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.