Evidence map›Paper›PMID 25573478›Full record

ArticleJournal of neuroinflammation2015

Retinal pericytes and cytomegalovirus infectivity: implications for HCMV-induced retinopathy and congenital ocular disease.

Irene Wilkerson, Joshua Laban, Johnathan M Mitchell, Nader Sheibani, Donald J Alcendor

Open access · goldAbstract read
In one paragraph

Article in Journal of neuroinflammation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed, 1 pooled it
2.8field-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

23 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.

  1. Pooled it
  2. Review
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  8. Review
  9. Review
  10. Observational
  11. Unique method for human villous trophoblasts isolation from placental tissue explants.Clinical obstetrics, gynecology and reproductive medicine · 2020
    Article
  12. Multifaceted roles of pericytes in central nervous system homeostasis and disease.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2020
    Review
  13. Review
  14. Blocking VEGF signaling augments interleukin-8 secretionInternational journal of ophthalmology · 2020
    Article
  15. Article
  16. Human Vascular Pericytes and Cytomegalovirus Pathobiology.International journal of molecular sciences · 2019
    Review
  17. Article
  18. Article
  19. Observational
  20. Article
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

5 authors at 1 institution in 1 country.

Irene WilkersonDepartment of Microbiology and Immunology, Center for AIDS Health Disparities Research, Meharry Medical College, School of Medicine, 1005 Dr DB Todd Jr Blvd, Nashville, TN, 37208, USA. imw0001@tigermail.auburn.edu.
Joshua LabanDepartment of Microbiology and Immunology, Center for AIDS Health Disparities Research, Meharry Medical College, School of Medicine, 1005 Dr DB Todd Jr Blvd, Nashville, TN, 37208, USA. jlaban12@email.mmc.edu.
Johnathan M MitchellDepartment of Microbiology and Immunology, Center for AIDS Health Disparities Research, Meharry Medical College, School of Medicine, 1005 Dr DB Todd Jr Blvd, Nashville, TN, 37208, USA. mitchell155@live.marshall.edu.
Nader SheibaniDepartment of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI, 53792, USA. nsheibanikar@wisc.edu.
Donald J AlcendorDepartment of Microbiology and Immunology, Center for AIDS Health Disparities Research, Meharry Medical College, School of Medicine, 1005 Dr DB Todd Jr Blvd, Nashville, TN, 37208, USA. dalcendor@mmc.edu.
Meharry Medical College · US

Funding

Technologies and Resources CoreU54MD007593 · NIMHD · MEHARRY MEDICAL COLLEGE · PI ADUNYAH, SAMUEL EVANS · 2012 to 2018
$24.7M
WYETH 303 STUDYP20RR011792 · NCRR · MEHARRY MEDICAL COLLEGE · PI TORRENTE, SANDRA L. · 1996 to 2009
$14.4M
TECHNOLOGIES AND RESOURCES FOR CORE LABORATORIESU54RR026140 · NCRR · MEHARRY MEDICAL COLLEGE · PI GOODWIN, JEFFREY SHAWN · 2009 to 2011
$12.9M
Meharry RCMI Program in Women's Health ResearchG12MD007586 · NIMHD · MEHARRY MEDICAL COLLEGE · PI HILDRETH, JAMES E · 2012 to 2016
$7.8M
Novel Antiangiogenic Peptides for Treatment of Exudative AMDR24EY022883 · NEI · UNIVERSITY OF WISCONSIN-MADISON · PI SHEIBANI, NADER · 2013 to 2017
$6.2M
Neurovascular Unit on a Chip: Regional Chemical Communication, Drug and Toxin ResponsesUH3TR000491 · NCATS · VANDERBILT UNIVERSITY · PI GHOSH, CHAITALI, JANIGRO, DAMIR · 2014 to 2016
$3.8M
Neurovascular Unit on a Chip: Chemical Communication, Drug and Toxin ResponsesUH2TR000491 · NCATS · VANDERBILT UNIVERSITY · PI JANIGRO, DAMIR, NISWENDER, KEVIN D · 2012 to 2013
$2.2M
NCATS NIH HHS 3UH2TR000491-02S1NCATS NIH HHS UH2 TR000491NCATS NIH HHS UH3 TR000491NCRR NIH HHS P20 RR011792NCRR NIH HHS P20RR011792NCRR NIH HHS U54 RR026140NCRR NIH HHS U54RR026140NEI NIH HHS R24 EY022883NIMHD NIH HHS G12 MD007586NIMHD NIH HHS U54 MD007593
6 · The paper itself

Abstract

backgroundHuman cytomegalovirus (HCMV) is the leading infectious cause of vision loss among congenitally infected children. Retinal pericytes play an essential role in maintaining retinal vascular and endothelial cell proliferation. However, the role of retinal pericytes in ocular HCMV pathogenesis is unknown.

methodsRetinal pericytes were exposed to clinical (SBCMV) and lab strains of HCMV; infectivity was analyzed by microscopy, immunofluorescence and qRT-PCR (reverse transcription polymerase chain reaction). Cytokine expression was examined by Luminex assay. Recombinant HCMV-GPF was used to examine viral replication kinetics. A Tricell culture model of the inner blood-retinal barrier (IBRB) was examined for cell type infectivity using immunohistochemistry.

resultsRetinal pericytes expressed the biomarker neuron-glial antigen 2. Antigenic expression profiles for several cytoskeletal, cell adhesion and inflammatory proteins were shared by both retinal and brain pericytes. Infected pericytes showed cytomegalic cytopathology and expressed mRNAs for the major immediate protein (MIE) and HCMV phosphorylated envelop protein 65. qRT-PCR analysis showed full lytic replication of HCMV in retinal pericytes. Pericytes exposed to SBCMV for 9 days expressed higher levels of vascular endothelial cell growth factor mRNA compared to controls. Luminex analysis of supernatants from SBCMV-infected retinal pericytes had increased levels of macrophage inflammatory protein-1α, beta-2 microglobulin (B2-m), matrix metalloproteinase-3 and -9 (MMP3/9), and lower levels of IL-6 and IL-8 compared to controls. At 24 hours post infection, pericytes expressed higher levels of IL-8, TIMP-1 (tissue inhibitor of metalloproteinase-1), and RANTES (regulated upon activation normal T cell-expressed and presumably secreted) but lower levels of MMP9. Time course analysis showed that both brain and retinal pericytes were more permissive for HCMV infection than other cellular components of the BBB (blood-brain barrier) and IBRB. Using a Tricell culture model of the IBRB (retinal endothelial, pericytes, Müller cells), retinal pericytes were most permissive for SBCMV infection. SBCMV infection of this IBRB Tricell mixture for 96 hours resulted in increased levels of IL-6, MMP9, and stem cell factor with a concomitant decrease in granulocyte-macrophage colony-stimulating factor and TNF-alpha.

conclusionIn retinal pericytes, HCMV induces proinflammatory and angiogenic cytokines. In the IBRB, pericytes likely serve as an amplification reservoir which contributes to retinal inflammation and angiogenesis.

Indexed as

AntigensBrainCell Adhesion MoleculesCells, CulturedChondroitin Sulfate Proteoglycan 4CytokinesCytomegalovirusFibronectinsGene Expression Regulation, ViralGreen Fluorescent ProteinsHumansNeovascularization, PathologicNeurogliaNeuronsPericytesProteoglycansAntigensCell Adhesion Moleculescell aggregation factorsChondroitin Sulfate Proteoglycan 4CytokinesFibronectinsGreen Fluorescent ProteinsProteoglycansRNA, MessengerVimentin

Identifiers

PMID25573478
PMCPMC4314746
OpenAlexW2100656102

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.