ArticleActa neuropathologica communications2018
EphrinB/EphB forward signaling in Müller cells causes apoptosis of retinal ganglion cells by increasing tumor necrosis factor alpha production in rat experimental glaucomatous model.
Article in Acta neuropathologica communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 42 citations in OpenAlex.
- Tumor Necrosis Factor Alpha-Mediated Interaction Between Microglia and Müller Cells Exacerbates Retinal Ganglion Cell Damage in Experimental Glaucoma.Neuroscience bulletin · 2026Article
- Multi-omic spatial effects on high-resolution AI-derived retinal thickness.Nature communications · 2025Article
- EPHB1 Protein Promoted the Progression of Prostate Adenocarcinoma Through Phosphorylating GSK3B and Activating EPHB1-GSK3B-SMAD3 Pathway.Human mutation · 2025Article
- Ephrin B1 Regulates Inflammatory Pathways in Retinal Müller Cells.Journal of diabetes and clinical research · 2024Article
- EphB1 causes retinal damage through inflammatory pathways in the retina and retinal Müller cells.Molecular vision · 2024Article
- Cellular Characterization and Interspecies Evolution of the Tree Shrew Retina across Postnatal Lifespan.Research (Washington, D.C.) · 2024Article
- Activation of multiple Eph receptors on neuronal membranes correlates with the onset of optic neuropathy.Eye and vision (London, England) · 2023Article
- FTO-mediated m6A modification alleviates autoimmune uveitis by regulating microglia phenotypes via the GPC4/TLR4/NF-κB signaling axis.Genes & diseases · 2023Article
- Activation of Multiple Eph Receptors on Neuronal Membranes Correlates with The Onset of Traumatic Optic Neuropathy.bioRxiv : the preprint server for biology · 2023Article
- The PANoptosis-related signature indicates the prognosis and tumor immune infiltration features of gliomas.Frontiers in molecular neuroscience · 2023Article
- P2X7/P2X4 Receptors Mediate Proliferation and Migration of Retinal Microglia in Experimental Glaucoma in Mice.Neuroscience bulletin · 2022Article
- Statins Inhibit the Gliosis of MIO-M1, a Müller Glial Cell Line Induced by TRPV4 Activation.International journal of molecular sciences · 2022Article
- Interplay between Müller cells and microglia aggravates retinal inflammatory response in experimental glaucoma.Journal of neuroinflammation · 2021Article
- TRPV4-induced Müller cell gliosis and TNF-α elevation-mediated retinal ganglion cell apoptosis in glaucomatous rats via JAK2/STAT3/NF-κB pathway.Journal of neuroinflammation · 2021Article
- Soluble tumor necrosis factor-alpha-induced hyperexcitability contributes to retinal ganglion cell apoptosis by enhancing Nav1.6 in experimental glaucoma.Journal of neuroinflammation · 2021Article
- Effects of a New Combination of Natural Extracts on Glaucoma-Related Retinal Degeneration.Foods (Basel, Switzerland) · 2021Article
- Eph Receptors and Ephrins in Retinal Diseases.International journal of molecular sciences · 2021Review
- Rac1 conditional deletion attenuates retinal ganglion cell apoptosis by accelerating autophagic flux in a mouse model of chronic ocular hypertension.Cell death & disease · 2020Article
- TNFα-Mediated Priming of Mesenchymal Stem Cells Enhances Their Neuroprotective Effect on Retinal Ganglion Cells.Investigative ophthalmology & visual science · 2020Article
- The peroxisome proliferator-activated receptor-β/δ antagonist GSK0660 mitigates retinal cell inflammation and leukostasis.Experimental eye research · 2020Article
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12 authors at 4 institutions in 1 country.
Funding
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Abstract
It was previously shown that EphB/ephrinB reverse signaling in retinal ganglion cells (RGCs) is activated and involved in RGC apoptosis in a rat chronic ocular hypertension (COH) model. In the present work, we first show that ephrinB/EphB forward signaling was activated in COH retinas, and RGC apoptosis in COH retinas was reduced by PP2, an inhibitor of ephrinB/EphB forward signaling. We further demonstrate that treatment of cultured Müller cells with ephrinB1-Fc, an EphB1 activator, or intravitreal injection of ephrinB1-Fc in normal rats induced an increase in phosphorylated EphB levels in these cells, indicating the activation of ephrinB/EphB forward signaling, similar to those in COH retinas. The ephrinB1-Fc treatment did not induce Müller cell gliosis, as evidenced by unchanged GFAP expression, but significantly up-regulated mRNA and protein levels of tumor necrosis factor-α (TNF-α) in Müller cells, thereby promoting RGC apoptosis. Production of TNF-α induced by the activation of ephrinB/EphB forward signaling was mediated by the NR2B subunit of NMDA receptors, which was followed by a distinct PI3K/Akt/NF-κB signaling pathway, as pharmacological interference of each step of this pathway caused a reduction of TNF-α production, thus attenuating RGC apoptosis. Functional analysis of forward and reverse signaling in such a unique system, in which ephrin and Eph exist respectively in a glial element and a neuronal element, is of theoretical importance. Moreover, our results also raise a possibility that suppression of ephrinB/EphB forward signaling may be a new strategy for ameliorating RGC apoptosis in glaucoma.
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