Evidence map›Paper›PMID 34750957›Full record

ArticleJournal of extracellular vesicles2021

Extracellular vesicles released by human retinal pigment epithelium mediate increased polarised secretion of drusen proteins in response to AMD stressors.

Miguel Flores-Bellver, Jason Mighty, Silvia Aparicio-Domingo, Kang V Li, Cui Shi, Jing Zhou, Hannah Cobb, Patrick McGrath, German Michelis, Patricia Lenhart and 8 more

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

Article in Journal of extracellular vesicles, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed, 1 pooled it
12.0field-weighted citation impact, top 1% 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

55 citing papers in PubMed, 1 synthesis or guideline pooled it, 87 citations in OpenAlex.

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  20. The RNA content of extracellular vesicles from gene-editedMolecular therapy. Methods & clinical development · 2025
    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

18 authors at 9 institutions in 1 country.

Miguel Flores-BellverCellSight Ocular Stem Cell and Regeneration Program, Department of Ophthalmology, Sue Anschutz-Rodgers Eye Center, University of Colorado, School of Medicine, Aurora, Colorado, USA.ORCID 0000-0003-3421-3699
Jason MightyLehman College, Bronx, New York, USA.
Silvia Aparicio-DomingoCellSight Ocular Stem Cell and Regeneration Program, Department of Ophthalmology, Sue Anschutz-Rodgers Eye Center, University of Colorado, School of Medicine, Aurora, Colorado, USA.
Kang V LiCellSight Ocular Stem Cell and Regeneration Program, Department of Ophthalmology, Sue Anschutz-Rodgers Eye Center, University of Colorado, School of Medicine, Aurora, Colorado, USA.
Cui ShiLehman College, Bronx, New York, USA.
Jing ZhouLehman College, Bronx, New York, USA.
Hannah CobbCellSight Ocular Stem Cell and Regeneration Program, Department of Ophthalmology, Sue Anschutz-Rodgers Eye Center, University of Colorado, School of Medicine, Aurora, Colorado, USA.
Patrick McGrathDepartment of Dermatology, University of Colorado School of Medicine, Aurora, Colorado, USA.
German MichelisSection of Protein Structure and Function, NEI, NIH, Bethesda, Maryland, USA.
Patricia LenhartCellSight Ocular Stem Cell and Regeneration Program, Department of Ophthalmology, Sue Anschutz-Rodgers Eye Center, University of Colorado, School of Medicine, Aurora, Colorado, USA.
Ganna BilousovaDepartment of Dermatology, University of Colorado School of Medicine, Aurora, Colorado, USA.
Søren HeisselProteomics Resource Center, The Rockefeller University, New York, New York, USA.
Michael J RudyDepartment of Neurology, University of Colorado School of Medicine, Aurora, Colorado, USA.
Christina CoughlanUniversity of Colorado Alzheimer's and Cognition Center, Department of Neurology, Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Andrew E GoodspeedDepartment of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
S Patricia BecerraSection of Protein Structure and Function, NEI, NIH, Bethesda, Maryland, USA.
Stephen RedentiLehman College, Bronx, New York, USA.
M Valeria Canto-SolerCellSight Ocular Stem Cell and Regeneration Program, Department of Ophthalmology, Sue Anschutz-Rodgers Eye Center, University of Colorado, School of Medicine, Aurora, Colorado, USA.
University of Colorado Anschutz Medical Campus · USThe Graduate Center, CUNY · USGates (United States) · USProtein Express (United States) · USUniversity of Colorado Denver · USColorado Neurological Institute · USLehman College · USRockefeller University · USUniversity of Colorado Cancer Center · US

Funding

Modeling Photoreceptor Migration in Biomimetic Microenvironments to Optimize TransplantationSC3GM113782 · NIGMS · HERBERT H. LEHMAN COLLEGE · PI REDENTI, STEPHEN M · 2015 to 2024
$898k
Photoreceptor integration via chemotactic honingR21EY026752 · NEI · CITY COLLEGE OF NEW YORK · PI VAZQUEZ, MARIBEL · 2016 to 2017
$431k
NEI NIH HHS 5R21EY026752-02NEI NIH HHS R21 EY026752NIGMS NIH HHS 5SC3GM113782NIGMS NIH HHS SC3 GM113782
6 · The paper itself

Abstract

Age-related macular degeneration (AMD) is a leading cause of blindness worldwide. Drusen are key contributors to the etiology of AMD and the ability to modulate drusen biogenesis could lead to therapeutic strategies to slow or halt AMD progression. The mechanisms underlying drusen biogenesis, however, remain mostly unknown. Here we demonstrate that under homeostatic conditions extracellular vesicles (EVs) secreted by retinal pigment epithelium (RPE) cells are enriched in proteins associated with mechanisms involved in AMD pathophysiology, including oxidative stress, immune response, inflammation, complement system and drusen composition. Furthermore, we provide first evidence that drusen-associated proteins are released as cargo of extracellular vesicles secreted by RPE cells in a polarised apical:basal mode. Notably, drusen-associated proteins exhibited distinctive directional secretion modes in homeostatic conditions and, differential modulation of this directional secretion in response to AMD stressors. These observations underpin the existence of a finely-tuned mechanism regulating directional apical:basal sorting and secretion of drusen-associated proteins via EVs, and its modulation in response to mechanisms involved in AMD pathophysiology. Collectively, our results strongly support an active role of RPE-derived EVs as a key source of drusen proteins and important contributors to drusen development and growth.

Indexed as

Cell PolarityCells, CulturedExtracellular VesiclesHumansInduced Pluripotent Stem CellsMacular DegenerationNicotineOrganoidsOxidative StressPhagocytosisProteinsReactive Oxygen SpeciesRetinal DrusenRetinal Pigment EpitheliumSecretomeSignal TransductionNicotineProteinsReactive Oxygen SpeciesAMDdrusenexosomesextracellular vesiclesmicrovesiclesproteomicsRPEstem cells

Identifiers

PMID34750957
PMCPMC8575963
OpenAlexW3211964353

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.