ArticleInvestigative ophthalmology & visual science2013
Alterations of retinal vasculature in cystathionine-Beta-synthase mutant mice, a model of hyperhomocysteinemia.
Article in Investigative ophthalmology & visual science, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 45 citations in OpenAlex.
- Review
- 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
- Dysfunctional one-carbon metabolism identifies vitamins BCell reports. Medicine · 2025Article
- Hyperhomocysteinemia-induced VCID results in visual deficits, reduced neuroinflammation and vascular alterations in the retina.Journal of neuroinflammation · 2025Article
- Deletion of myeloid HDAC3 promotes efferocytosis to ameliorate retinal ischemic injury.Journal of neuroinflammation · 2024Article
- Diabetic Retinopathy and Regulation of Mitochondrial Glutathione-Glutathione Peroxidase Axis in Hyperhomocysteinemia.Antioxidants (Basel, Switzerland) · 2024Article
- Homocysteine and mitochondrial quality control in diabetic retinopathy.Eye and vision (London, England) · 2024Article
- Warburg Effect as a Novel Mechanism for Homocysteine-Induced Features of Age-Related Macular Degeneration.International journal of molecular sciences · 2023Article
- Cystathionine β-synthase as novel endogenous regulator of lymphangiogenesis via modulating VEGF receptor 2 and 3.Communications biology · 2022Article
- Effect of long-term chronic hyperhomocysteinemia on retinal structure and function in the cystathionine-β-synthase mutant mouse.Experimental eye research · 2022Article
- Long-term functional correction of cystathionine β-synthase deficiency in mice by adeno-associated viral gene therapy.Journal of inherited metabolic disease · 2021Article
- Homocysteine and Age-Related Central Nervous System Diseases: Role of Inflammation.International journal of molecular sciences · 2021Review
- N-Methyl-D-aspartate receptor activation, novel mechanism of homocysteine-induced blood-retinal barrier dysfunction.Journal of molecular medicine (Berlin, Germany) · 2021Article
- Review
- Homocysteine Induces Inflammation in Retina and Brain.Biomolecules · 2020Article
- Homocysteine: A Potential Biomarker for Diabetic Retinopathy.Journal of clinical medicine · 2019Article
- Hydrogen sulfide improves postischemic neoangiogenesis in the hind limb of cystathionine-β-synthase mutant mice via PPAR-γ/VEGF axis.Physiological reports · 2018Article
- Epigenetic modifications in hyperhomocysteinemia: potential role in diabetic retinopathy and age-related macular degeneration.Oncotarget · 2018Article
- Hyperhomocysteinemia Alters Retinal Endothelial Cells Barrier Function and Angiogenic Potential via Activation of Oxidative Stress.Scientific reports · 2017Article
- Cystathionine β-synthase deficiency: Of mice and men.Molecular genetics and metabolism · 2017Review
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
purposeMice with moderate/severe hyperhomocysteinemia due to deficiency or absence of the cbs gene encoding cystathionine-beta-synthase (CBS) have marked retinal disruption, ganglion cell loss, optic nerve mitochondrial dysfunction, and ERG defects; those with mild hyperhomocysteinemia have delayed retinal morphological/functional phenotype. Excess homocysteine is a risk factor for cardiovascular diseases; however, it is not known whether excess homocysteine alters retinal vasculature.
methodsCbs(+/+), cbs(+/-), and cbs(-/-) mice (age ∼3 weeks) were subjected to angiography; retinas were harvested for cryosections, flat-mount preparations, or trypsin digestion and subjected to immunofluorescence microscopy to visualize vessels using isolectin-B4, to detect angiogenesis using anti-VEGF and anti-endoglin (anti-CD105) and activated glial cells (anti-glial fibrillary acidic protein [anti-GFAP]) and to investigate the blood-retinal barrier using the tight junction markers zonula occludens-1 (ZO-1) and occludin. Expression of vegf was determined by quantitative RT-PCR (qRT-PCR) and immunoblotting. Human retinal endothelial cells (HRECs) were treated with excess homocysteine to analyze permeability.
resultsAngiography revealed vascular leakage in cbs(-/-) mice; immunohistochemical analysis demonstrated vascular patterns consistent with ischemia; isolectin-B4 labeling revealed a capillary-free zone centrally and new vessels with capillary tufts midperipherally. This was associated with increased vegf mRNA and protein, CD105, and GFAP in cbs(-/-) retinas concomitant with a marked decrease in ZO-1 and occludin. Homocysteine-treated HRECs showed increased permeability.
conclusionsSevere elevation of homocysteine in cbs(-/-) mutant mice is accompanied by alterations in retinal vasculature (ischemia, neovascularization, and incompetent blood-retinal barrier). The marked disruption of retinal structure and decreased visual function reported in cbs(-/-) mice may reflect vasculopathy as well as neuropathy.
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