ArticleInvestigative ophthalmology & visual science2015
Retinal Ganglion Cell Loss and Mild Vasculopathy in Methylene Tetrahydrofolate Reductase (Mthfr)-Deficient Mice: A Model of Mild Hyperhomocysteinemia.
Article in Investigative ophthalmology & visual science, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 32 citations in OpenAlex.
- In search of a mouse model of Spaceflight Associated Neuro-ocular Syndrome using one-carbon genetics.Scientific reports · 2026Article
- Analysis of Keratoconus-Related Phenotypes in Two Pcsk1 Mouse Models.Translational vision science & technology · 2026Article
- Role and Relationship Between Homocysteine and HMolecular neurobiology · 2025Review
- Blood Based Vascular Marker Responses to OcufolinBiomarker insights · 2025Article
- Identification of Keratoconus-Related Phenotypes in Three Ppip5k2 Mouse Models.Investigative ophthalmology & visual science · 2024Article
- Diverse functions and pathogenetic role of Crumbs in retinopathy.Cell communication and signaling : CCS · 2024Review
- Homocysteine and Glaucoma.International journal of molecular sciences · 2023Review
- Effect of long-term chronic hyperhomocysteinemia on retinal structure and function in the cystathionine-β-synthase mutant mouse.Experimental eye research · 2022Article
- Inner retinal layer ischemia and vision loss after COVID-19 infection: A case report.Photodiagnosis and photodynamic therapy · 2021Article
- Software for Quantifying and Batch Processing Images of Brn3a and RBPMS Immunolabelled Retinal Ganglion Cells in Retinal Wholemounts.Translational vision science & technology · 2020Article
- PPIP5K2 and PCSK1 are Candidate Genetic Contributors to Familial Keratoconus.Scientific reports · 2019Article
- Hyperhomocysteinemia-induced death of retinal ganglion cells: The role of Müller glial cells and NRF2.Redox biology · 2019Article
- Expression Analysis of the Circular RNA Molecules in the Human Retinal Cells Treated with Homocysteine.Current eye research · 2019Article
- Excess homocysteine upregulates the NRF2-antioxidant pathway in retinal Müller glial cells.Experimental eye research · 2019Article
- Hypermethylation: Causes and Consequences in Skeletal Muscle Myopathy.Journal of cellular biochemistry · 2017Review
- Detailed electroretinographic findings in rd8 mice.Documenta ophthalmologica. Advances in ophthalmology · 2017Article
- Analysis of MTHFR, CBS, Glutathione, Taurine, and Hydrogen Sulfide Levels in Retinas of Hyperhomocysteinemic Mice.Investigative ophthalmology & visual science · 2017Article
- Long-term Characterization of Retinal Degeneration in Royal College of Surgeons Rats Using Spectral-Domain Optical Coherence Tomography.Investigative ophthalmology & visual science · 2017Article
- Homocysteine mediates transcriptional changes of the inflammatory pathway signature genes in human retinal pigment epithelial cells.International journal of ophthalmology · 2017Article
- Activation of the molecular chaperone, sigma 1 receptor, preserves cone function in a murine model of inherited retinal degeneration.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
purposeMethylenetetrahydrofolate reductase (Mthfr) is a key enzyme in homocysteine-methionine metabolism. We investigated Mthfr expression in retina and asked whether mild hyperhomocysteinemia, due to Mthfr deficiency, alters retinal neurovascular structure and function.
methodsExpression of Mthfr was investigated at the gene and protein level using quantitative (q) RT-PCR, in situ hybridization, immunoblotting, and immunohistochemistry (IHC). The Mthfr+/+ and Mthfr+/- mice were subjected to comprehensive evaluation using ERG, funduscopy, fluorescein angiography (FA), spectral-domain optical coherence tomography (SD-OCT), HPLC, and morphometric and IHC analysis of glial fibrillary acidic protein (GFAP) at 8 to 24 weeks.
resultsGene and protein analyses disclosed widespread retinal expression of Mthfr. Electroretinography (ERG) revealed a significant decrease in positive scotopic threshold response in retinas of Mthfr+/- mice at 24 weeks. Fundus examination in mice from both groups was normal; FA revealed areas of focal vascular leakage in 20% of Mthfr+/- mice at 12 to 16 weeks and 60% by 24 weeks. The SD-OCT revealed a significant decrease in nerve fiber layer (NFL) thickness at 24 weeks in Mthfr+/- compared to Mthfr+/+ mice. There was a 2-fold elevation in retinal hcy at 24 weeks in Mthfr+/- mice by HPLC and IHC. Morphometric analysis revealed an approximately 20% reduction in cells in the ganglion cell layer of Mthfr+/- mice at 24 weeks. The IHC indicated significantly increased GFAP labeling suggestive of Müller cell activation.
conclusionsMildly hyperhomocysteinemic Mthfr+/- mice demonstrate reduced ganglion cell function, thinner NFL, and mild vasculopathy by 24 weeks. The retinal phenotype is similar to that of hyperhomocysteinemic mice with deficiency of cystathionine-β-synthase (Cbs) reported earlier. The data support the hypothesis that hyperhomocysteinemia may be causative in certain retinal neurovasculopathies.
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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.