ArticleJournal of neuroinflammation2023
Empagliflozin targets Mfn1 and Opa1 to attenuate microglia-mediated neuroinflammation in retinal ischemia and reperfusion injury.
Article in Journal of neuroinflammation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 31 citations in OpenAlex.
- A dual-responsive CO-releasing nanogel ameliorates retinal ischemia-reperfusion injury by restoring mitochondrial homeostasis and attenuating cGAS-STING pathway activation.Materials today. Bio · 2026Article
- Nitrite increases mitofusin-1 levels to inhibit vascular smooth muscle cell proliferation and prevent intimal hyperplasia.Redox biology · 2026Article
- Mitochondrial Regulation of the NLRP3 Inflammasome in Diabetic Kidney Disease: From Mechanisms to Therapeutic Strategies.International journal of molecular sciences · 2026Review
- [Research progress on the mechanism of mitochondrial dynamics in diabetic foot ulcers and its related intervention strategies].Zhonghua shao shang yu chuang mian xiu fu za zhi · 2026Review
- Acarbose modulates microglial Pkm2 acetylation to reshape immunometabolism and preserve retinal neurons after ischemia-reperfusion.Journal of neuroinflammation · 2026Article
- Metabolic Reprogramming of Microglia in Neuroinflammation and Depression.International journal of molecular sciences · 2026Review
- Endoplasmic Reticulum-Mitochondrial Crosstalk in Calcium Regulation: Mechanistic Insights and Therapeutic Implications in Traumatic Brain Injury.Molecular neurobiology · 2026Review
- Empagliflozin Attenuates Global Cerebral Ischemic Injury After Cardiac Arrest Through Enhancing Ketone Body Oxidative Metabolism in Rats.Journal of the American Heart Association · 2026Article
- Sfrp2 in Microglia Inhibited S100a8-Mediated Neuroinflammation and Protected Neural Damage Following Retinal Ischemia-Reperfusion.Investigative ophthalmology & visual science · 2026Article
- Hypothermia Alleviates TBI-Induced Tau Hyperphosphorylation Through RBM3-Dependent GSK-3β and AMPK Pathways.Neurocritical care · 2026Article
- Organelle stress in NLRP3 inflammasome: a central mediator of neurodegenerative diseases.Molecular neurodegeneration · 2026Review
- The role of mitochondrial proteases in inflammation and immunity.Frontiers in immunology · 2026Review
- Applications of single-cell transcriptomics in glaucoma research: from the aqueous humor outflow pathway to retinal ganglion cell neurodegeneration.Frontiers in physiology · 2026Review
- Mitochondrial fission and fusion in inflammatory diseases: mechanisms and therapeutic implications.Journal of translational medicine · 2025Review
- Sodium-Glucose Cotransporter 2 Inhibitors: An Emerging Therapeutic Approach for Ischemic Stroke Management.CNS drugs · 2025Review
- Microglial Autophagy and Mitophagy in Ischemic Stroke: From Dual Roles to Therapeutic Modulation.Biology · 2025Review
- The role of microglia in the development of diabetic retinopathy and its potential clinical application.Human cell · 2025Review
- OPA1 mutations in dominant optic atrophy: domain-specific defects in mitochondrial fusion and apoptotic regulation.Journal of translational medicine · 2025Article
- OPA1 Enhances Microglial Amyloid-β Clearance and Alleviates Cognitive Impairments in an Alzheimer's Disease Model.Aging and disease · 2025Article
- Ganoderma lucidum polysaccharide attenuates retinal ischemia-reperfusion injury by regulating microglial M1/M2 polarization, suppressing neuroinflammation and inhibiting JAK2/STAT3 pathway.Biochemistry and biophysics reports · 2025Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
backgroundNeuroinflammation and mitochondrial dysfunction play crucial roles in retinal ischemia and reperfusion (IR) injury. Recent studies have identified mitochondrial function as a promising target for immunomodulation. Empagliflozin (EMPA), an anti-diabetic drug, has exhibited great potential as both an anti-inflammatory agent and a protector of mitochondrial health. This study aimed to assess the therapeutic efficacy of EMPA in retinal IR injury.
methodsTo evaluate the protective effects of EMPA, the drug was injected into the vitreous body of mice post-retinal IR. Single-cell RNA sequencing (scRNA-seq) analysis was conducted to uncover the underlying mechanisms, and the results were further validated through in vivo and in vitro experiments.
resultsEMPA effectively protected retinal ganglion cells (RGCs) from IR injury by attenuating local retinal inflammation. The scRNA-seq analysis revealed that EMPA downregulated the nucleotide-binding domain and leucine-rich repeat containing protein 3 (NLRP3) signaling pathway and restored mitochondrial dynamics by upregulating the expression of mitochondrial fusion-related genes, Mitofusin 1 (Mfn1) and optic atrophy 1 (Opa1). These findings were further corroborated by Western blotting. In vitro experiments provided additional insights, demonstrating that EMPA suppressed lipopolysaccharide (LPS)-induced cell inflammation and NLRP3 inflammasome activation. Moreover, EMPA enhanced mitochondrial fusion, neutralized mitochondrial reactive oxygen species (mtROS), and restored mitochondrial membrane potential (MMP) in BV2 microglia. Notably, genetic ablation of Mfn1 or Opa1 abolished the anti-inflammatory effects of EMPA.
conclusionsOur findings highlight the positive contribution of Mfn1 and Opa1 to the anti-inflammatory therapeutic effect of EMPA. By restoring mitochondrial dynamics, EMPA effectively mitigates microglia-mediated neuroinflammation and prevents RGC loss in retinal IR injury.
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