Evidence map›Paper›PMID 31740401›Full record

ArticleBiochimica et biophysica acta. Molecular basis of disease2020

Mechanisms of extracellular vesicle uptake in stressed retinal pigment epithelial cell monolayers.

Crystal Nicholson, Navjot Shah, Masaaki Ishii, Balasubramaniam Annamalai, Carlene Brandon, Jessalyn Rodgers, Tamara Nowling, Bärbel Rohrer

Open access · greenAbstract read
In one paragraph

Article in Biochimica et biophysica acta. Molecular basis of disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
1.5field-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

23 citing papers in PubMed, 43 citations in OpenAlex.

  1. Review
  2. Review
  3. Human Brain Endothelial Cell-Derived Extracellular Vesicles ReduceInternational journal of molecular sciences · 2025
    Article
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  5. Review
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  20. Emerging Role of Exosomes in Retinal Diseases.Frontiers in cell and developmental biology · 2021
    Review
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

8 authors at 2 institutions in 1 country.

Crystal NicholsonDepartments of Ophthalmology, Medical University of South Carolina, Charleston, SC 29425, United States of America.
Navjot ShahDepartments of Ophthalmology, Medical University of South Carolina, Charleston, SC 29425, United States of America.
Masaaki IshiiDepartments of Ophthalmology, Medical University of South Carolina, Charleston, SC 29425, United States of America.
Balasubramaniam AnnamalaiDepartments of Ophthalmology, Medical University of South Carolina, Charleston, SC 29425, United States of America.
Carlene BrandonDepartments of Ophthalmology, Medical University of South Carolina, Charleston, SC 29425, United States of America.
Jessalyn RodgersMedicine, Medical University of South Carolina, Charleston, SC 29425, United States of America.
Tamara NowlingMedicine, Medical University of South Carolina, Charleston, SC 29425, United States of America.
Bärbel RohrerDepartments of Ophthalmology, Medical University of South Carolina, Charleston, SC 29425, United States of America; Neurosciences, Medical University of South Carolina, Charleston, SC 29425, United States of America; Ralph H. Johnson VA Medical Center, Charleston, SC 29401, United States of America. Electronic address: rohrer@musc.edu.
Medical University of South Carolina · USRalph H. Johnson VA Medical Center · US

Funding

Alternative Pathway of Complement Activation in Age-Related Macular DegenerationR01EY019320 · NEI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI ROHRER, BAERBEL · 2010 to 2014
$2.1M
ECT Implants for Factor H Delivery in Models of AMDR01EY024581 · NEI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI ROHRER, BAERBEL · 2014 to 2016
$1.1M
RPE Cell Bystander Effects Contribute to AMD PathologyI01BX003050 · VA · RALPH H JOHNSON VA MEDICAL CENTER · PI ROHRER, BAERBEL · 2016 to 2024
–
Complement Factor H Haplotypes and Smoking in Age-Related Macular DegenerationI01RX000444 · VA · RALPH H JOHNSON VA MEDICAL CENTER · PI Baerbel Rohrer · 2011 to 2026
–
BLR&D Research Career Scientist Award for Dr. Barbel RohrerIK6BX004858 · VA · RALPH H JOHNSON VA MEDICAL CENTER · PI Baerbel Rohrer · 2020 to 2026
–
BLRD VA I01 BX003050BLRD VA IK6 BX004858NEI NIH HHS R01 EY019320NEI NIH HHS R01 EY024581RRD VA I01 RX000444
6 · The paper itself

Abstract

purposeExtracellular vesicles (EVs) can mediate long-distance communication in polarized RPE monolayers. Specifically, EVs from oxidatively stressed donor cells (stress EVs) rapidly reduced barrier function (transepithelial resistance, TER) in naïve recipient monolayers, when compared to control EVs. This effect on TER was dependent on dynamin-mediated EV uptake, which occurred rapidly with EVs from oxidatively stressed donor cells. Here, we further determined molecular mechanisms involved in uptake of EVs by naïve RPE cells.

methodsRPE cells were grown as monolayers in media supplemented with 1% FBS followed by transfer to FBS-free media. Cultures were used to collect control or stress EVs upon treatment with H

resultsClathrin-independent, lipid raft-mediated internalization was excluded as an uptake mechanism. Known ligand-receptor interactions involved in clathrin-dependent endocytosis include integrins and proteoglycans. Desialylated glycans and integrin-receptors on recipient cells were necessary for EV uptake and subsequent reduction of TER in recipient cells. Protein quantifications confirmed elevated levels of ligands and neuraminidase on stress EVs. However, control EVs could confer activity in the TER assay if exogenous neuraminidase or additional ligand was provided.

conclusionsIn summary, while EVs from both stressed cells and control contain cargo to communicate stress messages to naive RPE cells, stress EVs contain surface ligands that confer rapid uptake by recipient cells. We propose that EVs potentially contribute to RPE dysfunction in aging and disease.

Indexed as

Biological TransportCell LineClathrinEndocytosisEpithelial CellsExtracellular VesiclesHumansHydrogen PeroxideLigandsMembrane ProteinsNeuronsOxidative StressRetinal Pigment EpitheliumRetinal PigmentsClathrinHydrogen PeroxideLigandsMembrane ProteinsRetinal PigmentsAge-related macular degenerationAnnexin A2Extracellular vesiclesLigandsNeuraminidaseRetinal pigment epitheliumUptake mechanisms

Identifiers

PMID31740401
PMCPMC6954962
OpenAlexW2987323834

What OpenQuestion holds

Textmetadata
LicenceTDM
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.