ArticleExperimental eye research2019
Excess homocysteine upregulates the NRF2-antioxidant pathway in retinal Müller glial cells.
Article in Experimental eye research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 38 citations in OpenAlex.
- CR2-fH, A Targeted Inhibitor of Alternative Complement Pathway Reduces Dry AMD-Like Phenotype in AMD Patient iPSC-derived RPE Cells.Investigative ophthalmology & visual science · 2026Article
- Modulating One-Carbon Metabolism with B-Vitamins to Protect the Retinal Barrier and Prevent Retinal Degeneration.Nutrients · 2026Article
- Can Persistent Blue Light Exposure Cause a Molecular Shift in the Vitreous of Rodents?Scientifica · 2026Article
- Uncovering Hyperhomocysteinemia: Global Risk Patterns and Molecular Disruption in Brain and Vascular Health.Journal of neurochemistry · 2025Review
- Vitamins, Vascular Health and Disease.Nutrients · 2025Review
- Proteomic Alterations in Retinal Müller Glial Cells Lacking Interleukin-6 Receptor: A Comprehensive Analysis.Investigative ophthalmology & visual science · 2024Article
- An insight into role of amino acids as antioxidants via NRF2 activation.Amino acids · 2024Review
- Müller Glial Cells in the Macula: Their Activation and Cell-Cell Interactions in Age-Related Macular Degeneration.Investigative ophthalmology & visual science · 2024Review
- The Implication of a Polymorphism in the Methylenetetrahydrofolate Reductase Gene in Homocysteine Metabolism and Related Civilisation Diseases.International journal of molecular sciences · 2023Review
- Homocysteine and Glaucoma.International journal of molecular sciences · 2023Review
- Article
- Generation and characterization of a Müller-glial-cell-specific Il6ra knockout mouse to delineate the effects of IL-6 trans-signaling in the retina.Scientific reports · 2022Article
- Sigma-1 Receptor in Retina: Neuroprotective Effects and Potential Mechanisms.International journal of molecular sciences · 2022Review
- The Role of Organosulfur Compounds as Nrf2 Activators and Their Antioxidant Effects.Antioxidants (Basel, Switzerland) · 2022Review
- Sigma 1 Receptor Contributes to Astrocyte-Mediated Retinal Ganglion Cell Protection.Investigative ophthalmology & visual science · 2022Article
- Effect of long-term chronic hyperhomocysteinemia on retinal structure and function in the cystathionine-β-synthase mutant mouse.Experimental eye research · 2022Article
- Inhibiting the activation of MAPK (ERK1/2) in stressed Müller cells prevents photoreceptor degeneration.Theranostics · 2022Article
- Short-TermBioMed research international · 2022Article
- Sulforaphane Modulates the Inflammation and Delays Neurodegeneration on a Retinitis Pigmentosa Mice Model.Frontiers in pharmacology · 2022Article
- Homocysteine and Mitochondria in Cardiovascular and Cerebrovascular Systems.International journal of molecular sciences · 2020Review
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
This study evaluated the effects of elevated homocysteine (Hcy) on the oxidative stress response in retinal Müller glial cells. Elevated Hcy has been implicated in retinal diseases including glaucoma and optic neuropathy, which are characterized by retinal ganglion cell (RGC) loss. To understand the mechanisms of Hcy-induced RGC loss, in vitro and in vivo models have been utilized. In vitro isolated RGCs are quite sensitive to elevated Hcy levels, while in vivo murine models of hyperhomocysteinemia (HHcy) demonstrate a more modest RGC loss (∼20%) over a period of many months. This differential response to Hcy between isolated cells and the intact retina suggests that the retinal milieu invokes mechanisms that buffer excess Hcy. Oxidative stress has been implicated as a mechanism of Hcy-induced neuron loss and NRF2 is a transcription factor that plays a major role in regulating cytoprotective responses to oxidative stress. In the present study we investigated whether HHcy upregulates NRF2-mediated stress responses in Müller cells, the chief retinal glial cell responsible for providing trophic support to retinal neurons. Primary Müller cells were exposed to L-Hcy-thiolactone [50μM-10mM] and assessed for viability, reactive oxygen species (ROS), and glutathione (GSH) levels. Gene/protein levels of Nrf2 and levels of NRF2-regulated antioxidants (NQO1, CAT, SOD2, HMOX1, GPX1) were assessed in Hcy-exposed Müller cells. Unlike isolated RGCs, isolated Müller cells are viable over a wide range of Hcy concentrations [50 μM - 1 mM]. Moreover, when exposed to elevated Hcy, Müller cells demonstrate decreased oxidative stress and decreased ROS levels. GSH levels increased by ∼20% within 24 h exposure to Hcy. Molecular analyses revealed 2-fold increase in Nrf2 expression. Expression of antioxidant genes Nqo1, Cat, Sod2, Hmox1, Gpx1 increased significantly. The consequences of Hcy exposure were evaluated also in Müller cells harvested from Nrf2
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