ArticleThe American journal of pathology2014
Alterations of retinal vasculature in cystathionine-β-synthase heterozygous mice: a model of mild to moderate hyperhomocysteinemia.
Article in The American journal of pathology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 48 citations in OpenAlex.
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- Modulating One-Carbon Metabolism with B-Vitamins to Protect the Retinal Barrier and Prevent Retinal Degeneration.Nutrients · 2026Article
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- Combined Herbal Eye Drops Exhibit Neuroprotective and Intraocular Pressure-Reducing Effects in a Glaucoma Rat Model.Antioxidants (Basel, Switzerland) · 2025Article
- Single-cell sequencing systematically analyzed the mechanism of Emdogain on the restoration of delayed replantation periodontal membrane.International journal of oral science · 2025Article
- Hyperhomocysteinemia-induced VCID results in visual deficits, reduced neuroinflammation and vascular alterations in the retina.Journal of neuroinflammation · 2025Article
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- Chemistry of Hydrogen Sulfide-Pathological and Physiological Functions in Mammalian Cells.Cells · 2023Review
- The Role of Methionine-Rich Diet in Unhealthy Cerebrovascular and Brain Aging: Mechanisms and Implications for Cognitive Impairment.Nutrients · 2023Review
- Triciribine attenuates pathological neovascularization and vascular permeability in a mouse model of proliferative retinopathy.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2023Article
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- Warburg Effect as a Novel Mechanism for Homocysteine-Induced Features of Age-Related Macular Degeneration.International journal of molecular sciences · 2023Article
- Effect of long-term chronic hyperhomocysteinemia on retinal structure and function in the cystathionine-β-synthase mutant mouse.Experimental eye research · 2022Article
- Implication ofInternational journal of molecular sciences · 2021Article
- Homocysteine and Age-Related Central Nervous System Diseases: Role of Inflammation.International journal of molecular sciences · 2021Review
- Hydrogen Sulfide: Novel Endogenous and Exogenous Modulator of Oxidative Stress in Retinal Degeneration Diseases.Molecules (Basel, Switzerland) · 2021Review
- N-Methyl-D-aspartate receptor activation, novel mechanism of homocysteine-induced blood-retinal barrier dysfunction.Journal of molecular medicine (Berlin, Germany) · 2021Article
- Immunosubunit β5i Knockout Suppresses Neovascularization and Restores Autophagy in Retinal Neovascularization by Targeting ATG5 for Degradation.Investigative ophthalmology & visual science · 2020Article
- Characterization of hydrogen sulfide toxicity to human corneal stromal fibroblasts.Annals of the New York Academy of Sciences · 2020Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Mild to moderate hyperhomocysteinemia is prevalent in humans and is implicated in neurovascular diseases, including recently in certain retinal diseases. Herein, we used hyperhomocysteinemic mice deficient in the Cbs gene encoding cystathionine-β-synthase (Cbs(+/-)) to evaluate retinal vascular integrity. The Cbs(+/+) (wild type) and Cbs(+/-) (heterozygous) mice (aged 16 to 52 weeks) were subjected to fluorescein angiography and optical coherence tomography to assess vasculature in vivo. Retinas harvested for cryosectioning or flat mount preparations were subjected to immunofluorescence microscopy to detect blood vessels (isolectin-B4), angiogenesis [anti-vascular endothelial growth factor (VEGF) and anti-CD105], gliosis [anti-glial fibrillary acidic protein (GFAP)], pericytes (anti-neural/glial antigen 2), blood-retinal barrier [anti-zonula occludens protein 1 (ZO-1) and anti-occludin], and hypoxia [anti-pimonidazole hydrochloride (Hypoxyprobe-1)]. Levels of VEGF, GFAP, ZO-1, and occludin were determined by immunoblotting. Results of these analyses showed a mild vascular phenotype in young mice, which progressed with age. Fluorescein angiography revealed progressive neovascularization and vascular leakage in Cbs(+/-) mice; optical coherence tomography confirmed new vessels in the vitreous by 1 year. Immunofluorescence microscopy demonstrated vascular patterns consistent with ischemia, including a capillary-free zone centrally and new vessels with capillary tufts midperipherally in older mice. This was associated with increased VEGF, CD105, and GFAP and decreased ZO-1/occludin levels in the Cbs(+/-) retinas. Retinal vein occlusion was observed in some Cbs(+/-) mouse retinas. We conclude that mild to moderate elevation of homocysteine in Cbs(+/-) mice is accompanied by progressive alterations in retinal vasculature characterized by ischemia, neovascularization, incompetent blood-retinal barrier, and vascular occlusion.
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