Evidence map›Paper›PMID 20811045›Full record

ArticleInvestigative ophthalmology & visual science2011

The role of RPE cell-associated VEGF₁₈₉ in choroidal endothelial cell transmigration across the RPE.

Haibo Wang, Pete Geisen, Erika S Wittchen, Bradley King, Keith Burridge, Patricia A D'Amore, M Elizabeth Hartnett

Abstract read
In one paragraph

Article in Investigative ophthalmology & visual science, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
–field-weighted citation impact
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

28 citing papers in PubMed.

  1. Impact of aging on vascular ion channels: perspectives and knowledge gaps across major organ systems.American journal of physiology. Heart and circulatory physiology · 2023
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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

7 authors.

Haibo WangDepartment of Ophthalmology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Pete Geisen
Erika S Wittchen
Bradley King
Keith Burridge
Patricia A D'Amore
M Elizabeth Hartnett

Funding

Endothelial Transmigration in Neovascular Age-related Macular DegenerationR01EY017011 · NEI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI HARTNETT, MARY ELIZABETH RUTH · 2007 to 2025
$7.7M
Mechanisms of Angiogenesis of Retinopathy of PrematurityR01EY015130 · NEI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Mary Elizabeth Ruth Hartnett · 2005 to 2026
$7.6M
STRUCTURE/FUNCTION OF FOCAL ADHESIONSR01GM029860 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BURRIDGE, KEITH · 1985 to 2018
$6.7M
Role of RPE-derived VEGF in Choroid Development and StabilityR01EY015435 · NEI · SCHEPENS EYE RESEARCH INSTITUTE · PI D'AMORE, PATRICIA ANN · 2004 to 2013
$4.3M
NEI NIH HHS EY015435NEI NIH HHS R01 EY015130NEI NIH HHS R01 EY015435NEI NIH HHS R01 EY017011NIGMS NIH HHS 3-R01-GM029860-28SNIGMS NIH HHS GM029860NIGMS NIH HHS R01 GM029860
6 · The paper itself

Abstract

purposeTo determine the role of vascular endothelial growth factor 189 (VEGF₁₈₉) in choroidal endothelial cell (CEC) migration across the retinal pigment epithelium (RPE) and to explore the molecular mechanisms involved.

methodsUsing real-time PCR, the expression of VEGF splice variants VEGF₁₂₁, VEGF₁₆₅, and VEGF₁₈₉ was determined in human RPE from donor eyes, cultured human RPE in contact with CECs exposed to hydrogen peroxide (H₂O₂) or hypoxia, and RPE/choroid specimens from mice treated with laser to induce choroidal neovascularization (CNV). Activation of VEGF receptors (VEGFRs), phosphoinositol 3-kinase (PI-3K) or Rac1 was measured in CECs cocultured in contact with RPE exposed to peroxide or silenced for VEGF₁₈₉ expression. Migration of CECs across the RPE was determined using fluorescence microscopy.

resultsVEGF₁₈₉ expression was increased in human RPE from aged compared with young donor eyes and from mouse RPE/choroids after laser to induce CNV. VEGF₁₈₉ was also upregulated in human RPE challenged with peroxide, hypoxia, or cultured in contact with CECs. CEC migration across RPE was greater after RPE exposure to peroxide to induce VEGF₁₈₉; VEGFR2 and Rac1 activities were also increased in these CECs. When CECs were cocultured with RPE silenced for VEGF₁₈₉, VEGFR2 and Rac1 activities in CECs were significantly reduced, as was CEC migration across the RPE. Inhibition of Rac1 activity significantly inhibited CEC transmigration without affecting PI-3K activity.

conclusionsRPE-derived cell-associated VEGF₁₈₉ facilitates CEC transmigration by Rac1 activation independently of PI-3K signaling and may have importance in the development of neovascular AMD.

Indexed as

AdultAgedAgingAnimalsCells, CulturedChoroidChoroidal NeovascularizationCoculture TechniquesEndothelium, VascularGene SilencingHumansHydrogen PeroxideMiceMice, Inbred C57BLMice, TransgenicPhosphatidylinositol 3-KinasesHydrogen PeroxidePhosphatidylinositol 3-Kinasesrac1 GTP-Binding ProteinVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2VEGFA protein, human

Identifiers

PMID20811045
PMCPMC3053298

What OpenQuestion holds

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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.