ArticleJournal of neuroinflammation2024
Pathological high intraocular pressure induces glial cell reactive proliferation contributing to neuroinflammation of the blood-retinal barrier via the NOX2/ET-1 axis-controlled ERK1/2 pathway.
Article in Journal of neuroinflammation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- The bidirectional enigma of glaucoma and anxiety: from neuroinflammatory mechanisms to mind-body integrated therapies.Frontiers in psychiatry · 2025Pooled it
- NADPH oxidases in immunometabolism and disease pathology: mechanistic networks, pollutant triggers, and therapeutic frontiers.Cellular & molecular immunology · 2026Review
- Immunological drivers of oxidative stress in glaucoma: implications for antioxidant therapy.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2026Review
- tRNA-derived small RNAs in ocular neovascular diseases: A systematic review.Non-coding RNA research · 2026Review
- The Role of Nuclear Factor Erythroid 2-Related Factor 2 in the Crosstalk Between Oxidative Stress and M1/M2 Microglial Polarization Following Ischemic Stroke.Molecular neurobiology · 2026Review
- Dual role of microglia in glaucoma: Regulation of neuroinflammation and neuroregeneration.Neural regeneration research · 2026Article
- Review
- Axonopathy: mechanisms and potential therapeutic targets for neurodegenerative diseases.Translational neurodegeneration · 2026Review
- Review
- Identification and validation of a novel ferroptosis-related gene signature associated with inherited retinal degeneration in Rd10 mice.Scientific reports · 2026Article
- Circular RNA PTPN4 Contributes to Blood-Brain Barrier Disruption during Early Epileptogenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Research Advances in Glanimal Models of Glaucoma: Exploring Multidimensional Mechanisms and Novel Therapeutic Strategies.Pharmaceutics · 2026Review
- Age- and diet-dependent progression of retinal microvascular injury in GCK-MODY under metabolic stress.Frontiers in endocrinology · 2026Article
- Nox3 expression and function in retinal ganglion cells and Amacrine cells.Cellular and molecular life sciences : CMLS · 2025Article
- Bradykinin-bradykinin 2 receptor and oxidative stress.Annals of medicine · 2025Review
- Crosstalk Between Neuronal and Glial Cells in Diabetic Retinopathy: Mechanisms and Implications for Neurodegeneration.Molecular neurobiology · 2025Review
- Spatiotemporal Immune Dynamics in Experimental Retinal Ganglion Cell Injury Models.Immunity, inflammation and disease · 2025Review
- Genetically Predicted Immunocyte Phenotypes as Risk and Protective Factors in Glaucoma: An Exploratory Bidirectional Mendelian Randomization Study.Translational vision science & technology · 2025Article
- Potential role of nanopharmacology in reducing neuroinflammation associated with hypertension and metabolic disorders.World journal of experimental medicine · 2025Review
- HOCPCA Exerts Neuroprotection on Retinal Ganglion Cells by Binding to CaMKIIα and Modulating Oxidative Stress and Neuroinflammation in Experimental Glaucoma.Neuroscience bulletin · 2025Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNADPH oxidase (NOX), a primary source of endothelial reactive oxygen species (ROS), is considered a key event in disrupting the integrity of the blood-retinal barrier. Abnormalities in neurovascular-coupled immune signaling herald the loss of ganglion cells in glaucoma. Persistent microglia-driven inflammation and cellular innate immune system dysregulation often lead to deteriorating retinal degeneration. However, the crosstalk between NOX and the retinal immune environment remains unresolved. Here, we investigate the interaction between oxidative stress and neuroinflammation in glaucoma by genetic defects of NOX2 or its regulation via gp91ds-tat.
methodsEx vivo cultures of retinal explants from wildtype C57BL/6J and Nox2
resultsWe found that NOX2-specific deletion or activity inhibition effectively attenuated retinal oxidative stress, immune dysregulation, the internal blood-retinal barrier (iBRB) injury, neurovascular unit (NVU) dysfunction, RGC loss, and ON axonal degeneration following H-IOP. Mechanistically, we unveiled for the first time that NOX2-dependent ROS-driven pro-inflammatory signaling, where NOX2/ROS induces endothelium-derived endothelin-1 (ET-1) overexpression, which activates the ERK1/2 signaling pathway and mediates the shift of microglia activation to a pro-inflammatory M1 phenotype, thereby triggering a neuroinflammatory outburst.
conclusionsCollectively, we demonstrate for the first time that NOX2 deletion or gp91ds-tat inhibition attenuates iBRB injury and NVU dysfunction to rescue glaucomatous RGC loss and ON axon degeneration, which is associated with inhibition of the ET-1/ERK1/2-transduced shift of microglial cell activation toward a pro-inflammatory M1 phenotype, highlighting NOX2 as a potential target for novel neuroprotective therapies in glaucoma management.
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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.