ArticleJournal of neuroinflammation2015
Monomethyl fumarate promotes Nrf2-dependent neuroprotection in retinal ischemia-reperfusion.
Article in Journal of neuroinflammation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 81 citations in OpenAlex.
- Fumarate and Its Esters: Physiology, Pathology, Molecular Mechanisms, Diseases, and Therapy.MedComm · 2026Review
- Protective effects ofHistology and histopathology · 2026Article
- Melatonin reprograms antioxidant defenses to suppress ferroptosis via Homer1a/mGluR1-Nrf2/xCT signaling after retinal ischemia-reperfusion.Redox biology · 2026Article
- Spatial multi-omics unveils sphingolipid metabolic reprogramming within the retinal pathological niche.iMeta · 2026Article
- Prospects of DNA nanotechnology in stroke repair and regeneration.Communications biology · 2026Review
- Hydroxycarboxylic acid receptor 2 (GPR109A) and retinopathies: pathways and prospects.Frontiers in medicine · 2026Review
- Crosstalk Between Neuronal and Glial Cells in Diabetic Retinopathy: Mechanisms and Implications for Neurodegeneration.Molecular neurobiology · 2025Review
- Review
- DDO1002, an NRF2-KEAP1 inhibitor, improves hematopoietic stem cell aging and stress response.Life medicine · 2024Article
- Suppression of inner blood-retinal barrier breakdown and pathogenic Müller glia activation in ischemia retinopathy by myeloid cell depletion.Journal of neuroinflammation · 2024Article
- The Multifaceted Roles of NRF2 in Cancer: Friend or Foe?Antioxidants (Basel, Switzerland) · 2024Review
- Oxidative stress in the eye and its role in the pathophysiology of ocular diseases.Redox biology · 2023Review
- Article
- Drug-Repurposing Strategy for Dimethyl Fumarate.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Monomethyl fumarate prevents alloimmune rejection in mouse heart transplantation by inducing tolerogenic dendritic cells.Acta biochimica et biophysica Sinica · 2023Article
- Neuroprotective Effects of Erinacine A on an Experimental Model of Traumatic Optic Neuropathy.International journal of molecular sciences · 2023Article
- Review
- Dimethyl Fumarate Triggers the Antioxidant Defense System in Human Retinal Endothelial Cells through Nrf2 Activation.Antioxidants (Basel, Switzerland) · 2022Article
- Müller Glial Expression of REDD1 Is Required for Retinal Neurodegeneration and Visual Dysfunction in Diabetic Mice.Diabetes · 2022Article
- Targeting NLRP3 Inflammasome With Nrf2 Inducers in Central Nervous System Disorders.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundRetinal ischemia results in neuronal degeneration and contributes to the pathogenesis of multiple blinding diseases. Recently, the fumaric acid ester dimethyl fumarate (DMF) has been FDA-approved for the treatment of multiple sclerosis, based on its neuroprotective and anti-inflammatory effects. Its potential role as a neuroprotective agent for retinal diseases has received little attention. In addition, DMF's mode of action remains elusive, although studies have suggested nuclear factor erythroid 2-related factor 2 (Nrf2) activation as an important mechanism. Here we investigated the neuroprotective role of monomethyl fumarate (MMF), the biologically active metabolite of DMF, in retinal ischemia-reperfusion (I/R) injury, and examined the role of Nrf2 in mediating MMF action.
methodsWild-type C57BL/6J and Nrf2 knockout (KO) mice were subjected to 90 min of retinal ischemia followed by reperfusion. Mice received daily intraperitoneal injection of MMF. Inflammatory gene expression was measured using quantitative reverse transcription PCR (qRT-PCR) at 48 h after I/R injury. Seven days after I/R, qRT-PCR for Nrf2 target gene expression, immunostaining for Müller cell gliosis and cell loss in the ganglion cell layer (GCL), and electroretinography for retinal function were performed.
resultsThe results of this study confirmed that MMF reduces retinal neurodegeneration in an Nrf2-dependent manner. MMF treatment significantly increased the expression of Nrf2-regulated antioxidative genes, suppressed inflammatory gene expression, reduced Müller cell gliosis, decreased neuronal cell loss in the GCL, and improved retinal function measured by electroretinogram (ERG) after retinal I/R injury in wild-type mice. Importantly, these MMF-mediated beneficial effects were not observed in Nrf2 KO mice.
conclusionsThese results indicate that fumaric acid esters (FAEs) exert a neuronal protective function in the retinal I/R model and further validate Nrf2 modulation as a major mode of action of FAEs. This suggests that DMF and FAEs could be a potential therapeutic agent for activation of the Nrf2 pathway in retinal and possibly systemic diseases.
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