ArticleCell death and differentiation2018
Necroptosis in microglia contributes to neuroinflammation and retinal degeneration through TLR4 activation.
Article in Cell death and differentiation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers.
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Who cites it
117 citing papers in PubMed, 173 citations in OpenAlex.
- Metabolic reprogramming of microglia: Effects on development, disease, and therapeutic potential.Neural regeneration research · 2026Article
- cGAS-STING pathway modulation: A new hope for neural regeneration.Neural regeneration research · 2026Article
- Exploring Endotoxemia in Age-Related Macular Degeneration, Glaucoma, and Diabetic Retinopathy.Investigative ophthalmology & visual science · 2026Review
- Bacillus cereus Induces Necroptosis in Microglia via the RIPK1/3-MLKL Pathway.MicrobiologyOpen · 2026Article
- TDP-43 pathology triggers neuroinflammation and cognitive impairment by inducing microglial necroptosis.EMBO molecular medicine · 2026Article
- Microglial polarization in retinal neovascularization: Friend or foe?Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2026Review
- Z-DNA binding protein 1 mediates necroptotic cell death in primary murine microglia following herpes simplex virus-1 infection.Journal of neurovirology · 2026Article
- Sfrp2 in Microglia Inhibited S100a8-Mediated Neuroinflammation and Protected Neural Damage Following Retinal Ischemia-Reperfusion.Investigative ophthalmology & visual science · 2026Article
- GPR40 Attenuates Age-Related Macular Degeneration by Suppressing Retinal Microglial NLRP3 Inflammasome Activation Via ERK Signaling.Inflammation · 2026Article
- Dietary dihydroquercetin alleviates age-related cognitive impairment in association with modulation of apoptosis and pyroptosis pathways.Frontiers in pharmacology · 2026Article
- Emerging Roles of Regulated Cell Death-mediated Inflammation in Pathophysiology of Ocular Diseases.Journal of ophthalmic & vision research · 2026Review
- Multiomics Profiling Identifies Tlr4 as a Therapeutic Target of Necroptosis in Spinal Cord Injury.Mediators of inflammation · 2026Article
- Evaluation of the Protective Effect of Vitamin B17 Against the Potential UV Damage UsingInsects · 2025Article
- Retinal Pigment Epithelium Extracellular Vesicles Induce Microglia Polarization in MERTK-Associated Retinal Degeneration.Investigative ophthalmology & visual science · 2025Article
- Induction of immunogenic necroptosis by shikonin in drug‑resistant head and neck squamous cell carcinoma cells.Oncology reports · 2025Article
- Autophagy-Induced Microglial Death Contributes to Neuroinflammation in Acute Optic Nerve Injury.Investigative ophthalmology & visual science · 2025Article
- Microglial Necroptosis Mediated by RIPK3 Leads to Retinal Ganglion Cell Apoptosis Through the Release of FGF2 After Ischemia/Reperfusion.Journal of molecular neuroscience : MN · 2025Article
- Early-stage diabetic retinopathy: gut-metabolic triggers, immune-neurodegeneration, and interventions.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2025Review
- Suppression of necroptosis-driven cell death and inflammation in hypoxic neuroblastoma (SH-SY5Y) cells by necrostatin-1.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- RIPK3 Contributes to Thyroid Hormone-Induced Photoreceptor Degeneration.International journal of molecular sciences · 2025Article
57 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inflammation has emerged to be a critical mechanism responsible for neural damage and neurodegenerative diseases. Microglia, the resident innate immune cells in retina, are implicated as principal components of the immunological insult to retinal neural cells. The involvement of microglia in retinal inflammation is complex and here we propose for the first time that necroptosis in microglia triggers neuroinflammation and exacerbates retinal neural damage and degeneration. We found microglia experienced receptor-interacting protein kinase 1 (RIP1)- and RIP3-dependent necroptosis not only in the retinal degenerative rd1 mice, but also in the acute retinal neural injury mice. The necroptotic microglia released various pro-inflammatory cytokines and chemokines, such as tumor necrosis factor-α and chemokine (C-C motif) ligand 2, which orchestrated the retinal inflammation. Importantly, necroptosis blockade using necrostatin-1 could suppress microglia-mediated inflammation, rescue retinal degeneration or prevent neural injury in vivo. Meanwhile, cultured microglia underwent RIP1/3-mediated necroptosis and the necroptotic microglia produced large amounts of pro-inflammatory cytokines in response to lipopolysaccharide or oxidative stress in vitro. Mechanically, TLR4 deficiency ameliorated microglia necroptosis with decreased expression levels of machinery molecules RIP1 and RIP3, and suppressed retinal inflammation, suggesting that TLR4 signaling was required in microglia necroptosis-mediated inflammation. Thus, we proposed that microglia experienced necroptosis through TLR4 activation, promoting an inflammatory response that serves to exacerbate considerable neural damage and degeneration. Necroptosis blockade therefore emerged as a novel therapeutic strategy for tempering microglia-mediated neuroinflammation and ameliorating neural injury and neurodegenerative diseases.
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