ArticleCell death & disease2023
RIP3-mediated microglial necroptosis promotes neuroinflammation and neurodegeneration in the early stages of diabetic retinopathy.
Article in Cell death & disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- Neuroprotective Agents for Photoreceptor Rescue Following Experimental Retinal Detachment in Rodents: A Systematic Review.Investigative ophthalmology & visual science · 2026Pooled it
- Anti-Vascular Endothelial Growth Factor Combined with Dexamethasone Implant Therapy for Macular Edema: A Randomized Controlled Trial.Drug design, development and therapy · 2026Trial
- Necroptosis and the RIPK1-RIPK3-MLKL pathway in chronic kidney disease: mechanisms, crosstalk, and therapeutic opportunities.Renal failure · 2026Review
- ZBP1 in Neuroinflammation and Neurodegeneration: Z-Nucleic-Acid Sensing, RHIM Signalling and Therapeutic Targeting.International journal of molecular sciences · 2026Review
- GSK'872 mitigates ischemia-reperfusion injury in rat lung transplants by regulating PANoptosis and inflammation in cell type specific manner.Cell communication and signaling : CCS · 2026Article
- Role of Programmed Cell Death Pathways in Mediating Epithelial Wound Healing and Its Defects in Diabetic Corneas.Investigative ophthalmology & visual science · 2026Article
- TDP-43 pathology triggers neuroinflammation and cognitive impairment by inducing microglial necroptosis.EMBO molecular medicine · 2026Article
- Programmed cell death: a promising management for Alzheimer's disease.Apoptosis : an international journal on programmed cell death · 2026Review
- 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
- PANoptosis in diabetic retinopathy: immunological insights into mechanisms and translational therapies.Frontiers in immunology · 2026Review
- Emerging Roles of Regulated Cell Death-mediated Inflammation in Pathophysiology of Ocular Diseases.Journal of ophthalmic & vision research · 2026Review
- Generation of dual mouse models of retinal degeneration with slow and rapid progression driven by ectopic RIP3 expression.PloS one · 2026Article
- MLKL Modulates Necroptosis and Neuroinflammation in a Mouse Model of MS.Inflammation · 2025Article
- Targeting the gut-retina axis: mechanistic insights and therapeutic prospects for diabetic retinopathy.Inflammopharmacology · 2025Review
- Breakthroughs in diabetic retinopathy diagnosis and treatment using preclinical research models: current progress and future directions.Annals of medicine · 2025Review
- HLA-A drives diabetic retinopathy pathogenesis: multi-omics integration reveals resveratrol's therapeutic potential via immunomodulation.Journal of translational medicine · 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
- Diabetic retinopathy and Alzheimer's disease: Convergence of the unfolded protein response in neurodegeneration.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Structure-based design of potent and selective inhibitors targeting RIPK3 for eliminating on-target toxicity in vitro.Nature communications · 2025Article
- Single-cell analysis identifies MKI67Journal of translational medicine · 2025Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Diabetic retinopathy (DR) is a leading cause of blindness that poses significant public health concerns worldwide. Increasing evidence suggests that neuroinflammation plays a key role in the early stages of DR. Microglia, long-lived immune cells in the central nervous system, can become activated in response to pathological insults and contribute to retinal neuroinflammation. However, the molecular mechanisms of microglial activation during the early stages of DR are not fully understood. In this study, we used in vivo and in vitro assays to investigate the role of microglial activation in the early pathogenesis of DR. We found that activated microglia triggered an inflammatory cascade through a process called necroptosis, a newly discovered pathway of regulated cell death. In the diabetic retina, key components of the necroptotic machinery, including RIP1, RIP3, and MLKL, were highly expressed and mainly localized in activated microglia. Knockdown of RIP3 in DR mice reduced microglial necroptosis and decreased pro-inflammatory cytokines. Additionally, blocking necroptosis with the specific inhibitor GSK-872 improved retinal neuroinflammation and neurodegeneration, as well as visual function in diabetic mice. RIP3-mediated necroptosis was activated and contributed to inflammation in BV2 microglia under hyperglycaemic conditions. Our data demonstrate the importance of microglial necroptosis in retinal neuroinflammation related to diabetes and suggest that targeting necroptosis in microglia may be a promising therapeutic strategy for the early stages of DR.
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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.