Evidence map›Paper›PMID 21873678›Full record

ArticleInvestigative ophthalmology & visual science2011

The small GTPase Rap1 is a novel regulator of RPE cell barrier function.

Erika S Wittchen, M Elizabeth Hartnett

Open access · bronzeAbstract 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 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.4field-weighted citation impact, top 21% 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

19 citing papers in PubMed, 31 citations in OpenAlex.

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  3. Prostaglandin EFrontiers in pharmacology · 2025
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  16. Activation of Rap1 inhibits NADPH oxidase-dependent ROS generation in retinal pigment epithelium and reduces choroidal neovascularization.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2014
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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

2 authors at 1 institution in 1 country.

Erika S WittchenDepartment of Cell and Developmental Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
M Elizabeth Hartnett
University of North Carolina at Chapel Hill · US

Funding

University of Utah, Core Vision Research GrantP30EY014800 · NEI · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI PAUL STEVEN BERNSTEIN · 2005 to 2026
$14.6M
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
STRUCTURE/FUNCTION OF FOCAL ADHESIONSR01GM029860 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BURRIDGE, KEITH · 1985 to 2018
$6.7M
NEI NIH HHS P30 EY014800NEI NIH HHS R01 EY017011NIGMS NIH HHS 3-R01-GM029860-28SNIGMS NIH HHS R01 GM029860NIGMS NIH HHS R01-GM029860
6 · The paper itself

Abstract

purposeTo determine whether the small GTPase Rap1 regulates the formation and maintenance of the retinal pigment epithelial (RPE) cell junctional barrier.

methodsAn in vitro model was used to study RPE barrier properties. To dissect the role of Rap1, two techniques were used to inhibit Rap1 function: overexpression of RapGAP, which acts as a negative regulator of endogenous Rap1 activity, and treatment with engineered, adenovirally-transduced microRNAs to knockdown Rap1 protein expression. Transepithelial electrical resistance (TER) and real-time cellular analysis (RTCA) of impedance were used as readouts for barrier properties. Immunofluorescence microscopy was used to visualize localization of cadherins under steady state conditions and also during junctional reassembly after calcium switch. Finally, choroidal endothelial cell (CEC) migration across RPE monolayers was quantified under conditions of Rap1 inhibition in RPE.

resultsKnockdown of Rap1 or inhibition of its activity in RPE reduces TER and electrical impedance of the RPE monolayers. The loss of barrier function is also reflected by the mislocalization of cadherins and formation of gaps within the monolayer. TER measurement and immunofluorescent staining of cadherins after a calcium switch indicate that junctional reassembly kinetics are also impaired. Furthermore, CEC transmigration is significantly higher in Rap1-knockdown RPE monolayers compared with control.

conclusionsRap1 GTPase is an important regulator of RPE cell junctions, and is required for maintenance of barrier function. This observation that RPE monolayers lacking Rap1 allow greater transmigration of CECs suggests a possible role for potentiating choroidal neovascularization during the pathology of neovascular age-related macular degeneration.

Indexed as

AdenoviridaeBlood-Retinal BarrierCadherinsCell LineCell MovementChoroidElectric ImpedanceEndothelium, VascularGene Knockout TechniquesGene SilencingHumansMicroRNAsMicroscopy, Fluorescencerap1 GTP-Binding ProteinsRetinal Pigment EpitheliumCadherinsMicroRNAsrap1 GTP-Binding Proteins

Identifiers

PMID21873678
PMCPMC3183976
OpenAlexW2151655742

What OpenQuestion holds

Textmetadata
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.