Evidence map›Paper›PMID 25016930›Full record

ArticleThe American journal of pathology2014

Alterations of retinal vasculature in cystathionine-β-synthase heterozygous mice: a model of mild to moderate hyperhomocysteinemia.

Amany Tawfik, Shanu Markand, Mohamed Al-Shabrawey, Jamie N Mayo, Jason Reynolds, Shawn E Bearden, Vadivel Ganapathy, Sylvia B Smith

Open access · bronzeAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
3.1field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

40 citing papers in PubMed, 48 citations in OpenAlex.

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  15. Implication ofInternational journal of molecular sciences · 2021
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 1 country.

Amany TawfikDepartment of Cellular Biology and Anatomy, Medical College of Georgia, Georgia Regents University, Augusta, Georgia; James and Jean Culver Vision Discovery Institute, Georgia Regents University, Augusta, Georgia.
Shanu MarkandDepartment of Cellular Biology and Anatomy, Medical College of Georgia, Georgia Regents University, Augusta, Georgia; James and Jean Culver Vision Discovery Institute, Georgia Regents University, Augusta, Georgia.
Mohamed Al-ShabraweyJames and Jean Culver Vision Discovery Institute, Georgia Regents University, Augusta, Georgia; Department of Oral Biology and Anatomy, Medical College of Georgia, Georgia Regents University, Augusta, Georgia; Department of Ophthalmology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia.
Jamie N MayoDepartment of Biological Sciences, Idaho State University, Pocatello, Idaho.
Jason ReynoldsDepartment of Biological Sciences, Idaho State University, Pocatello, Idaho.
Shawn E BeardenDepartment of Biological Sciences, Idaho State University, Pocatello, Idaho.
Vadivel GanapathyJames and Jean Culver Vision Discovery Institute, Georgia Regents University, Augusta, Georgia; Department of Biochemistry and Molecular Biology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia.
Sylvia B SmithDepartment of Cellular Biology and Anatomy, Medical College of Georgia, Georgia Regents University, Augusta, Georgia; James and Jean Culver Vision Discovery Institute, Georgia Regents University, Augusta, Georgia; Department of Ophthalmology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia. Electronic address: sbsmith@gru.edu.
Augusta University · USIdaho State University · USDiscovery Institute · US

Funding

Role of homocysteine in retinal diseaseR01EY012830 · NEI · MEDICAL COLLEGE OF GEORGIA (MCG) · PI SMITH, SYLVIA B. · 2000 to 2016
$4.4M
Diabetic retinopathy: sigma receptor 1 (??R1) as a novel therapeutic target.R01EY014560 · NEI · MEDICAL COLLEGE OF GEORGIA (MCG) · PI SMITH, SYLVIA B. · 2004 to 2013
$2.7M
Role of lipoxygenase pathway in early microvascular dysfunction during diabetic rR01EY023315 · NEI · AUGUSTA UNIVERSITY · PI AL-SHABRAWEY, MOHAMED AL-SAYED · 2013 to 2017
$1.8M
NEI NIH HHS R01 EY012830NEI NIH HHS R01 EY014560NEI NIH HHS R01 EY023315
6 · The paper itself

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.

Indexed as

Disease Models, AnimalAnimalsCystathionine beta-SynthaseHeterozygoteHyperhomocysteinemiaMiceMice, Mutant StrainsMicroscopy, FluorescenceReal-Time Polymerase Chain ReactionRetinal NeovascularizationRetinal VesselsCystathionine beta-Synthase

Identifiers

PMID25016930
PMCPMC4188277
OpenAlexW2191654248

What OpenQuestion holds

Textmetadata
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Registered trials

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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.