ArticleInvestigative ophthalmology & visual science2011
The role of N-methyl-D-aspartate receptor activation in homocysteine-induced death of retinal ganglion cells.
Article in Investigative ophthalmology & visual science, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 2 of them syntheses that pooled it.
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Who cites it
42 citing papers in PubMed, 2 syntheses or guidelines pooled it, 97 citations in OpenAlex.
- Relationship between homocysteine level and diabetic retinopathy: a systematic review and meta-analysis.Diagnostic pathology · 2014Pooled it
- Plasma homocysteine, serum folic acid, serum vitamin B12, serum vitamin B6, MTHFR and risk of pseudoexfoliation glaucoma: a meta-analysis.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2012Pooled it
- Molecular and Mechanistic Divergence of Seizures in Pediatric Acute Lymphoblastic Leukemia: CNS Infiltration Versus Chemotherapy-Induced Neurotoxicity.International journal of molecular sciences · 2026Review
- Association of serum and vitreous homocysteine and uric acid concentrations with post-vitrectomy prognosis in patients with proliferative diabetic retinopathy.World journal of diabetes · 2026Article
- Unveiling the role of CaMKII in retinal degeneration: from biological mechanism to therapeutic strategies.Cell & bioscience · 2024Review
- Association Between High Blood Folate Levels and Glaucoma in a Representative Korean Population.Investigative ophthalmology & visual science · 2024Article
- Defective quality control autophagy in Hyperhomocysteinemia promotes ER stress and consequent neuronal apoptosis through proteotoxicity.Cell communication and signaling : CCS · 2023Article
- Homocysteine and Glaucoma.International journal of molecular sciences · 2023Review
- Promotion of axon regeneration and protection on injured retinal ganglion cells by rCXCL2.Inflammation and regeneration · 2023Article
- CaBiomolecules · 2023Article
- Mild Hyperhomocysteinemia Causes Anxiety-like Behavior and Brain Hyperactivity in Rodents: Are ATPase and Excitotoxicity by NMDA Receptor Overstimulation Involved in this Effect?Cellular and molecular neurobiology · 2022Article
- Effect of long-term chronic hyperhomocysteinemia on retinal structure and function in the cystathionine-β-synthase mutant mouse.Experimental eye research · 2022Article
- Macular Pigment Response to Lutein, Zeaxanthin, and Meso-zeaxanthin Supplementation in Open-Angle Glaucoma: A Randomized Controlled Trial.Ophthalmology science · 2021Article
- Involvements of Hyperhomocysteinemia in Neurological Disorders.Metabolites · 2021Review
- N-Methyl-D-aspartate receptor activation, novel mechanism of homocysteine-induced blood-retinal barrier dysfunction.Journal of molecular medicine (Berlin, Germany) · 2021Article
- Neuroprotection Against NMDA-Induced Retinal Damage by Philanthotoxin-343 Involves Reduced Nitrosative Stress.Frontiers in pharmacology · 2021Article
- Review
- Relationship between homocysteine levels, anterior chamber depth, and pseudoexfoliation glaucoma in patients with pseudoexfoliation.International ophthalmology · 2020Article
- Spermine oxidase: A promising therapeutic target for neurodegeneration in diabetic retinopathy.Pharmacological research · 2019Review
- Hyperhomocysteinemia leads to exacerbation of ischemic brain damage: Role of GluN2A NMDA receptors.Neurobiology of disease · 2019Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
purposeElevated plasma homocysteine has been implicated in glaucoma, a vision disorder characterized by retinal ganglion cell death. The toxic potential of homocysteine to ganglion cells is known, but the mechanisms are not clear. A mechanism of homocysteine-induced death of cerebral neurons is via N-methyl-D-aspartate (NMDA) receptor overstimulation, leading to excess calcium influx and oxidative stress. This study examined the role of the NMDA receptor in homocysteine-mediated ganglion cell death.
methodsPrimary mouse ganglion cells were used for these experiments. NMDA receptor stimulation by homocysteine was determined by patch clamp analysis and fluorescent detection of intracellular calcium. NMDA receptor involvement in homocysteine-mediated cell death was determined through assessment of lactate dehydrogenase release and TUNEL analysis. These experiments used the NMDA receptor blocker MK-801. Induction of reactive species superoxide, nitric oxide, and peroxynitrite was measured by electron paramagnetic resonance spectroscopy, chemiluminescent nitric oxide detection, and immunoblotting for nitrotyrosine, respectively.
results50 μM homocysteine stimulated the NMDA receptor in presence of 100 μM glycine. Homocysteine induced 59.67 ± 4.89% ganglion cell death that was reduced to 19.87 ± 3.03% with cotreatment of 250 nM MK-801. Homocysteine elevated intracellular calcium ∼7-fold, which was completely prevented by MK-801. Homocysteine treatment increased superoxide and nitric oxide levels by ∼40% and ∼90%, respectively, after 6 hours. Homocysteine treatment elevated peroxynitrite by ∼85% after 9 hours.
conclusionsThese experiments provide compelling evidence that homocysteine induces retinal ganglion cell toxicity through direct NMDA receptor stimulation and implicate, for the first time, the induction of oxidative stress as a potent mechanism of homocysteine-mediated ganglion cell death.
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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.