Evidence map›Paper›PMID 25657312›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2015

Nanoparticle-mediated expression of a Wnt pathway inhibitor ameliorates ocular neovascularization.

Zhongxiao Wang, Rui Cheng, Kyungwon Lee, Puneet Tyagi, Lexi Ding, Uday B Kompella, Jing Chen, Xun Xu, Jian-Xing Ma

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

Article in Arteriosclerosis, thrombosis, and vascular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
1.8field-weighted citation impact, top 17% 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

27 citing papers in PubMed, 39 citations in OpenAlex.

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  13. 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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  17. Wnt Signaling in vascular eye diseases.Progress in retinal and eye research · 2019
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 5 institutions in 2 countries.

Zhongxiao WangFrom the Department of Ophthalmology, Shanghai First People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China (Z.W., X.X.); Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City (Z.W., R.C., K.L., L.D., J.-x.M.); Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Denver, Aurora (P.T., U.B.K.); Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, China (L.D.); and Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, MA (J.C.).
Rui ChengFrom the Department of Ophthalmology, Shanghai First People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China (Z.W., X.X.); Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City (Z.W., R.C., K.L., L.D., J.-x.M.); Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Denver, Aurora (P.T., U.B.K.); Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, China (L.D.); and Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, MA (J.C.).
Kyungwon LeeFrom the Department of Ophthalmology, Shanghai First People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China (Z.W., X.X.); Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City (Z.W., R.C., K.L., L.D., J.-x.M.); Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Denver, Aurora (P.T., U.B.K.); Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, China (L.D.); and Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, MA (J.C.).
Puneet TyagiFrom the Department of Ophthalmology, Shanghai First People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China (Z.W., X.X.); Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City (Z.W., R.C., K.L., L.D., J.-x.M.); Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Denver, Aurora (P.T., U.B.K.); Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, China (L.D.); and Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, MA (J.C.).
Lexi DingFrom the Department of Ophthalmology, Shanghai First People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China (Z.W., X.X.); Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City (Z.W., R.C., K.L., L.D., J.-x.M.); Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Denver, Aurora (P.T., U.B.K.); Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, China (L.D.); and Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, MA (J.C.).
Uday B KompellaFrom the Department of Ophthalmology, Shanghai First People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China (Z.W., X.X.); Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City (Z.W., R.C., K.L., L.D., J.-x.M.); Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Denver, Aurora (P.T., U.B.K.); Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, China (L.D.); and Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, MA (J.C.).
Jing ChenFrom the Department of Ophthalmology, Shanghai First People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China (Z.W., X.X.); Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City (Z.W., R.C., K.L., L.D., J.-x.M.); Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Denver, Aurora (P.T., U.B.K.); Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, China (L.D.); and Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, MA (J.C.).
Xun XuFrom the Department of Ophthalmology, Shanghai First People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China (Z.W., X.X.); Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City (Z.W., R.C., K.L., L.D., J.-x.M.); Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Denver, Aurora (P.T., U.B.K.); Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, China (L.D.); and Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, MA (J.C.). jian-xing-ma@ouhsc.edu drxuxun@sjtu.edu.cn.
Jian-Xing MaFrom the Department of Ophthalmology, Shanghai First People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China (Z.W., X.X.); Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City (Z.W., R.C., K.L., L.D., J.-x.M.); Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Denver, Aurora (P.T., U.B.K.); Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, China (L.D.); and Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, MA (J.C.). jian-xing-ma@ouhsc.edu drxuxun@sjtu.edu.cn.
Central South University · CNShanghai First People's Hospital · CNXiangya Hospital Central South University · CNUniversity of Colorado Denver · USUniversity of Montana · US

Funding

THE ROLE OF COMPLEX 1 IN MITOCHONDRIAL DYSFUNCTION & FREE RADICAL PROD IN TYPE 1P20RR024215 · NCRR · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI XIE, ZHONGLIN · 2007 to 2011
$11.7M
Project 5 VEGF Signaling in PhotoreceptorsP20GM104934 · NIGMS · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI HAYS, FRANKLIN ALAN · 2012 to 2016
$10.8M
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
RORalpha mediates chronic subretinal inflammation associated with AMDR01EY024963 · NEI · BOSTON CHILDREN'S HOSPITAL · PI CHEN, JING · 2015 to 2025
$4.2M
The wnt signaling pathway in choroidal neovascularizationR01EY018659 · NEI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI MA, JIAN-XING · 2009 to 2019
$3.7M
NCRR NIH HHS P20 RR024215NEI NIH HHS EY012231NEI NIH HHS EY018659NEI NIH HHS EY019309NEI NIH HHS EY024963NEI NIH HHS R01 EY012231NEI NIH HHS R01 EY018659NEI NIH HHS R01 EY019309NEI NIH HHS R01 EY024963NIGMS NIH HHS GM104934NIGMS NIH HHS P20 GM104934
6 · The paper itself

Abstract

objectiveThe deficiency of very low-density lipoprotein receptor resulted in Wnt signaling activation and neovascularization in the retina. The present study sought to determine whether the very low-density lipoprotein receptor extracellular domain (VLN) is responsible for the inhibition of Wnt signaling in ocular tissues. APPROACH AND

resultsA plasmid expressing the soluble VLN was encapsulated with poly(lactide-co-glycolide acid) to form VLN nanoparticles (VLN-NP). Nanoparticles containing a plasmid expressing the low-density lipoprotein receptor extracellular domain nanoparticle were used as negative control. MTT, modified Boyden chamber, and Matrigel (™) assays were used to evaluate the inhibitory effect of VLN-NP on Wnt3a-stimulated endothelial cell proliferation, migration, and tube formation. Vldlr(-/-) mice, oxygen-induced retinopathy, and alkali burn-induced corneal neovascularization models were used to evaluate the effect of VLN-NP on ocular neovascularization. Wnt reporter mice (BAT-gal), Western blotting, and luciferase assay were used to evaluate Wnt pathway activity. Our results showed that VLN-NP specifically inhibited Wnt3a-induced endothelial cell proliferation, migration, and tube formation. Intravitreal injection of VLN-NP inhibited abnormal neovascularization in Vldlr(-/-), oxygen-induced retinopathy, and alkali burn-induced corneal neovascularization models, compared with low-density lipoprotein receptor extracellular domain nanoparticle. VLN-NP significantly inhibited the phosphorylation of low-density lipoprotein receptor-related protein 6, the accumulation of β-catenin, and the expression of vascular endothelial growth factor in vivo and in vitro.

conclusionsTaken together, these results suggest that the soluble VLN is a negative regulator of the Wnt pathway and has antiangiogenic activities. Nanoparticle-mediated expression of VLN may thus represent a novel therapeutic approach to treat pathological ocular angiogenesis and potentially other vascular diseases affected by Wnt signaling.

Indexed as

NanoparticlesWnt Signaling PathwayAnimalsbeta CateninCell MovementCell ProliferationCells, CulturedCorneaCorneal NeovascularizationDisease Models, AnimalHumansIntravitreal InjectionsLactic AcidLow Density Lipoprotein Receptor-Related Protein-6Mice, Inbred C57BLMice, Knockoutbeta CateninLactic AcidLow Density Lipoprotein Receptor-Related Protein-6Polyglycolic AcidPolylactic Acid-Polyglycolic Acid CopolymerReceptors, LDLVascular Endothelial Growth Factor AVLDL receptorWnt3A ProteineyenanoparticleneovascularizationVLDLRWnt

Identifiers

PMID25657312
PMCPMC4376607
OpenAlexW2150063144

What OpenQuestion holds

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Read underepoch 390

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.