Evidence map›Paper›PMID 26476672›Full record

ArticleJournal of translational medicine2015

Wnt signaling in age-related macular degeneration: human macular tissue and mouse model.

Jingsheng Tuo, Yujuan Wang, Rui Cheng, Yichao Li, Mei Chen, Fangfang Qiu, Haohua Qian, Defen Shen, Rosana Penalva, Heping Xu and 2 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of translational medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
2.1field-weighted citation impact, top 13% 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

36 citing papers in PubMed, 48 citations in OpenAlex.

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  17. Soluble very low-density lipoprotein receptor (sVLDLR) inhibits fibrosis in neovascular age-related macular degeneration.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 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

12 authors at 4 institutions in 2 countries.

Jingsheng TuoLaboratory of Immunology, National Eye Institute, National Institutes of Health, 10 Center Drive, Bldg. 10, Rm. 10N103, NIH/NEI, Bethesda, MD, 20892-1857, USA. tuoj@csr.nih.gov.
Yujuan WangLaboratory of Immunology, National Eye Institute, National Institutes of Health, 10 Center Drive, Bldg. 10, Rm. 10N103, NIH/NEI, Bethesda, MD, 20892-1857, USA. yujuanwang2013@gmail.com.
Rui ChengDepartment of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. rui-cheng@ouhsc.edu.
Yichao LiVisual Function Core, National Eye Institute, National Institutes of Health, Bethesda, MD, USA. yichao.li@nih.gov.
Mei ChenCentre for Experimental Medicine, Queen's University Belfast, Belfast, UK. m.chen@qub.ac.uk.
Fangfang QiuDepartment of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. Jian-Xing-Ma@ouhsc.edu.
Haohua QianVisual Function Core, National Eye Institute, National Institutes of Health, Bethesda, MD, USA. haohua.qian@nih.gov.
Defen ShenLaboratory of Immunology, National Eye Institute, National Institutes of Health, 10 Center Drive, Bldg. 10, Rm. 10N103, NIH/NEI, Bethesda, MD, 20892-1857, USA. defen.shen@gmail.com.
Rosana PenalvaCentre for Experimental Medicine, Queen's University Belfast, Belfast, UK. heping.xu@qub.ac.uk.
Heping XuCentre for Experimental Medicine, Queen's University Belfast, Belfast, UK. heping.xu@qub.ac.uk.
Jian-Xing MaDepartment of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. Jian-Xing-Ma@ouhsc.edu.
Chi-Chao ChanLaboratory of Immunology, National Eye Institute, National Institutes of Health, 10 Center Drive, Bldg. 10, Rm. 10N103, NIH/NEI, Bethesda, MD, 20892-1857, USA. chanc@nei.nih.gov.
National Eye Institute · USQueen's University Belfast · GBUniversity of Oklahoma Health Sciences Center · USNational Institutes of Health · US

Funding

Visual Function CoreZICEY000503 · NEI · NATIONAL EYE INSTITUTE · PI QIAN, HAOHUA · 2011 to 2025
$12.3M
A new pathogenic mechanism for diabetic retinopathyR01EY019309 · NEI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI Jian-Xing Jay Ma · 2009 to 2026
$6.1M
STUDIES OF RPE65R01EY012231 · NEI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI MA, JIAN-XING, MOISEYEV, GENNADIY · 1998 to 2021
$5.7M
The wnt signaling pathway in choroidal neovascularizationR01EY018659 · NEI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI MA, JIAN-XING · 2009 to 2019
$3.7M
Evaluation of Visual Function in Animal ModelsZIAEY000530 · NEI · NATIONAL EYE INSTITUTE · PI QIAN, HAOHUA · 2013 to 2025
$1.8M
NEI NIH HHS EY012231NEI NIH HHS EY018659NEI NIH HHS EY019309NEI NIH HHS R01 EY012231NEI NIH HHS R01 EY018659NEI NIH HHS R01 EY019309
6 · The paper itself

Abstract

backgroundThe wingless-type MMTV integration site (Wnt) signaling is a group of signal transduction pathways. In canonical Wnt pathway, Wnt ligands bind to low-density lipoprotein receptor-related protein 5 or 6 (LRP5 or LRP6), resulting in phosphorylation and activation of the receptor. We hypothesize that canonical Wnt pathway plays a role in the retinal lesion of age-related macular degeneration (AMD), a leading cause of irreversible central visual loss in elderly.

methodsWe examined LRP6 phosphorylation and Wnt signaling cascade in human retinal sections and plasma kallistatin, an endogenous inhibitor of the Wnt pathway in AMD patients and non-AMD subjects. We also used the Ccl2 (-/-) /Cx3cr1 (-/-) /rd8 and Ccl2 (-/-) /Cx3cr1 (gfp/gfp) mouse models with AMD-like retinal degeneration to further explore the involvement of Wnt signaling activation in the retinal lesions in those models and to preclinically evaluate the role of Wnt signaling suppression as a potential therapeutic option for AMD.

resultsWe found higher levels of LRP6 (a key Wnt signaling receptor) protein phosphorylation and transcripts of the Wnt pathway-targeted genes, as well as higher beta-catenin protein in AMD macula compared to controls. Kallistatin was decreased in the plasma of AMD patients. Retinal non-phosphorylated-β-catenin and phosphorylated-LRP6 were higher in Ccl2 (-/-) /Cx3cr1 (-/-) /rd8 mice than that in wild type. Intravitreal administration of an anti-LRP6 antibody slowed the progression of retinal lesions in Ccl2 (-/-) /Cx3cr1 (-/-) /rd8 and Ccl2 (-/-) /Cx3cr1 (gfp/gfp) mice. Electroretinography of treated eyes exhibited larger amplitudes compared to controls in both mouse models. A2E, a retinoid byproduct associated with AMD was lower in the treated eyes of Ccl2 (-/-) /Cx3cr1 (-/-) /rd8 mice. Anti-LRP6 also suppressed the expression of Tnf-α and Icam-1 in Ccl2 (-/-) /Cx3cr1 (-/-) /rd8 retinas.

conclusionsWnt signaling may be disturbed in AMD patients, which could contribute to the retinal inflammation and increased A2E levels found in AMD. Aberrant activation of canonical Wnt signaling might also contribute to the focal retinal degenerative lesions of mouse models with Ccl2 and Cx3cr1 deficiency, and intravitreal administration of anti-LRP6 antibody could be beneficial by deactivating the canonical Wnt pathway.

Indexed as

Gene Expression RegulationAgedAgingAnimalsChemokine CCL2CX3C Chemokine Receptor 1Disease Models, AnimalElectroretinographyFemaleHumansIntravitreal InjectionsLow Density Lipoprotein Receptor-Related Protein-6Macular DegenerationMaleMiceMice, KnockoutCCL2 protein, humanCcl2 protein, mouseChemokine CCL2CX3C Chemokine Receptor 1CX3CR1 protein, humanCx3cr1 protein, mousekallistatinLow Density Lipoprotein Receptor-Related Protein-6LRP6 protein, humanLrp6 protein, mouseReceptors, ChemokineSerpinsWnt Proteins

Identifiers

PMID26476672
PMCPMC4609061
OpenAlexW2148385501

What OpenQuestion holds

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LicenceCC BY
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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.