Evidence map›Paper›PMID 38108061›Full record

ArticleJournal of extracellular biology2023

Polarized Desmosome and Hemidesmosome Shedding via Small Extracellular Vesicles is an Early Indicator of Outer Blood-Retina Barrier Dysfunction.

Belinda J Hernandez, Nikolai P Skiba, Karolina Plössl, Madison Strain, Yutao Liu, Daniel Grigsby, Una Kelly, Martha A Cady, Vikram Manocha, Arvydas Maminishkis and 7 more

Erratum issuedOpen access · diamondAbstract read
In one paragraph

Article in Journal of extracellular biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
2.5field-weighted citation impact, top 11% 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

16 citing papers in PubMed, 17 citations in OpenAlex.

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  7. The RNA content of extracellular vesicles from gene-editedMolecular therapy. Methods & clinical development · 2025
    Article
  8. Article
  9. Rekindling Vision: Innovative Strategies for Treating Retinal Degeneration.International journal of molecular sciences · 2025
    Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 6 institutions in 2 countries.

Belinda J HernandezDepartment of Ophthalmology, Duke Eye Center, Duke University, Durham, NC 27710, USA.
Nikolai P SkibaDepartment of Ophthalmology, Duke Eye Center, Duke University, Durham, NC 27710, USA.
Karolina PlösslInstitute of Human Genetics, University of Regensburg, 93053 Regensburg, Germany.
Madison StrainDuke Molecular Physiology Institute, Department of Medicine, Duke University, Durham, NC 27710, USA.
Yutao LiuDepartment of Cellular Biology and Anatomy, Augusta University, Augusta, GA 30912, USA.
Daniel GrigsbyDepartment of Ophthalmology, Duke Eye Center, Duke University, Durham, NC 27710, USA.
Una KellyDepartment of Ophthalmology, Duke Eye Center, Duke University, Durham, NC 27710, USA.
Martha A CadyDepartment of Ophthalmology, Duke Eye Center, Duke University, Durham, NC 27710, USA.
Vikram ManochaDepartment of Ophthalmology, Duke Eye Center, Duke University, Durham, NC 27710, USA.
Arvydas MaminishkisOphthalmic Genetics and Visual Function Branch, Section on Epithelial and Retinal Physiology and Disease, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
TeddiJo WatkinsDepartment of Ophthalmology, Duke Eye Center, Duke University, Durham, NC 27710, USA.
Sheldon S MillerOphthalmic Genetics and Visual Function Branch, Section on Epithelial and Retinal Physiology and Disease, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Allison Ashley-KochDuke Molecular Physiology Institute, Department of Medicine, Duke University, Durham, NC 27710, USA.
W Daniel StamerDepartment of Ophthalmology, Duke Eye Center, Duke University, Durham, NC 27710, USA.
Bernhard H F WeberInstitute of Human Genetics, University of Regensburg, 93053 Regensburg, Germany.
Catherine Bowes RickmanDepartment of Ophthalmology, Duke Eye Center, Duke University, Durham, NC 27710, USA.
Mikael KlingebornDepartment of Ophthalmology, Duke Eye Center, Duke University, Durham, NC 27710, USA.
Duke University · USNational Institutes of Health · USAnimal Welfare Institute · USAugusta University · USUniversity Hospital Regensburg · DEUniversity of Regensburg · DE

Funding

VISION RESEARCHP30EY005722 · NEI · DUKE UNIVERSITY · PI W Daniel Stamer · 1985 to 2026
$19.3M
eNOS-Dependent Mechanoregulation of Intraocular PressureR01EY022359 · NEI · DUKE UNIVERSITY · PI STAMER, W DANIEL · 2012 to 2025
$5.6M
Caveolae-Based Mechanosensors for Conventional Outflow RegulationR01EY028608 · NEI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI MICHAEL H ELLIOTT, W Daniel Stamer · 2018 to 2026
$3.8M
Module 3: Gene Expression/ProteomicsP30EY031631 · NEI · AUGUSTA UNIVERSITY · PI Xingjun Fan · 2020 to 2026
$3.6M
Gene Discovery in Familial KeratoconusR01EY023242 · NEI · DUKE UNIVERSITY · PI LIU, YUTAO · 2013 to 2023
$3.4M
Complement factor H modulates lipoprotein clearance in AMDR01EY031748 · NEI · DUKE UNIVERSITY · PI BOWES RICKMAN, CATHERINE · 2020 to 2024
$2.8M
Estrogen and its Receptor in Intraocular Pressure RegulationR01EY032960 · NEI · MAYO CLINIC ROCHESTER · PI Yutao Liu · 2023 to 2026
$1.6M
The Role of RPE-derived Exosomes in Deposit Formation and ECM ModulationR21EY033057 · NEI · MC LAUGHLIN RESEARCH INSTITUTE · PI KLINGEBORN, MIKAEL · 2021 to 2022
$447k
RPE Exosomes in Age-related Macular DegenerationF31EY033170 · NEI · DUKE UNIVERSITY · PI HERNANDEZ, BELINDA J · 2021 to 2024
$91k
NEI NIH HHS F31 EY033170NEI NIH HHS P30 EY005722NEI NIH HHS P30 EY031631NEI NIH HHS R01 EY022359NEI NIH HHS R01 EY028608NEI NIH HHS R01 EY031748NEI NIH HHS R01 EY032960NEI NIH HHS R21 EY033057
6 · The paper itself

Abstract

The retinal pigmented epithelium (RPE) constitutes the outer blood-retinal barrier, enables photoreceptor function of the eye, and is constantly exposed to oxidative stress. As such, dysfunction of the RPE underlies pathology leading to development of age-related macular degeneration (AMD), the leading cause of vision loss among the elderly in industrialized nations. A major responsibility of the RPE is to process photoreceptor outer segments, which relies on the proper functioning of its endocytic pathways and endosomal trafficking. Exosomes and other extracellular vesicles (EVs) from RPE are an essential part of these pathways and may be early indicators of cellular stress. To test the role of small EVs (sEVs) including exosomes, that may underlie the early stages of AMD, we used a polarized primary RPE cell culture model under chronic subtoxic oxidative stress. Unbiased proteomic analyses of highly purified basolateral sEVs from oxidatively stressed RPE cultures revealed changes in proteins involved in epithelial barrier integrity. There were also significant changes in proteins accumulating in the basal-side sub-RPE extracellular matrix during oxidative stress, that could be prevented with an inhibitor of sEV release. Thus, chronic subtoxic oxidative stress in primary RPE cultures induces changes in sEV content, including basal-side specific desmosome and hemidesmosome shedding via sEVs. These findings provide novel biomarkers of early cellular dysfunction and opportunity for therapeutic intervention in age-related retinal diseases (e.g., AMD).

Indexed as

age-related macular degeneration (AMD)exosomeoxidative stresspolarizedproteomicsretinal pigmented epithelium (RPE)small extracellular vesicle (sEV)

Identifiers

PMID38108061
PMCPMC10720597
OpenAlexW4387575448

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.