Evidence map›Paper›PMID 35239183›Full record

ArticleThe Journal of pathology2022

Increased cell stiffness contributes to complement-mediated injury of choroidal endothelial cells in a monkey model of early age-related macular degeneration.

Andrea P Cabrera, Jonathan Stoddard, Irene Santiago Tierno, Nikolaos Matisioudis, Mahesh Agarwal, Lauren Renner, Neha Palegar, Martha Neuringer, Trevor McGill, Kaustabh Ghosh

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

Article in The Journal of pathology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
3.3field-weighted citation impact, top 8% 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

6 citing papers in PubMed, 16 citations in OpenAlex.

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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

10 authors at 4 institutions in 1 country.

Andrea P CabreraDepartment of Bioengineering, University of California, Riverside, CA, USA.
Jonathan StoddardDivision of Neuroscience, Oregon National Primate Research Center, Oregon Health and Sciences University, Beaverton, OR, USA.
Irene Santiago TiernoDepartment of Ophthalmology, University of California, Los Angeles, CA, USA.
Nikolaos MatisioudisDoheny Eye Institute, Pasadena, CA, USA.
Mahesh AgarwalDepartment of Ophthalmology, University of California, Los Angeles, CA, USA.
Lauren RennerDivision of Neuroscience, Oregon National Primate Research Center, Oregon Health and Sciences University, Beaverton, OR, USA.
Neha PalegarDepartment of Bioengineering, University of California, Riverside, CA, USA.
Martha NeuringerDivision of Neuroscience, Oregon National Primate Research Center, Oregon Health and Sciences University, Beaverton, OR, USA.
Trevor McGillDivision of Neuroscience, Oregon National Primate Research Center, Oregon Health and Sciences University, Beaverton, OR, USA.
Kaustabh GhoshDepartment of Bioengineering, University of California, Riverside, CA, USA.ORCID 0000-0001-8185-9180
Oregon National Primate Research Center · USUniversity of California, Riverside · USUniversity of California, Los Angeles · USDoheny Eye Institute · US

Funding

Upgrade of confocal microscopy at the Oregon National Primate Research CenterP51OD011092 · OD · OREGON HEALTH & SCIENCE UNIVERSITY · PI Bonnie J. Nagel · 2012 to 2026
$203.9M
Proteomics CoreP30EY010572 · NEI · OREGON HEALTH & SCIENCE UNIVERSITY · PI Kate E Keller · 1995 to 2026
$19.4M
Dietary Factors in Retinal Aging and Macular DiseaseR01EY028141 · NEI · OREGON HEALTH & SCIENCE UNIVERSITY · PI NEURINGER, MARTHA · 2018 to 2020
$1.5M
Laser Scanning Confocal MicroscopeS10RR024585 · NCRR · OREGON HEALTH & SCIENCE UNIVERSITY · PI CORNEA, ANDA N. · 2008 to 2008
$443k
NCRR NIH HHS S10 RR024585NEI NIH HHS P30 EY010572NEI NIH HHS R01 EY028141NIH HHS P51 OD011092
6 · The paper itself

Abstract

Age-related macular degeneration (AMD) is the leading cause of blindness in the aging population. Yet no therapies exist for ~85% of all AMD patients who have the dry form that is marked by degeneration of the retinal pigmented epithelium (RPE) and underlying choroidal vasculature. As the choroidal vessels are crucial for RPE development and maintenance, understanding how they degenerate may lead to effective therapies for dry AMD. One likely causative factor for choroidal vascular loss is the cytolytic membrane attack complex (MAC) of the complement pathway that is abundant on choroidal vessels of humans with early dry AMD. To examine this possibility, we studied the effect of complement activation on choroidal endothelial cells (ECs) isolated from a rhesus monkey model of early AMD that, we report, exhibits MAC deposition and choriocapillaris endothelial loss similar to that seen in human early AMD. Treatment of choroidal ECs from AMD eyes with complement-competent normal human serum caused extensive actin cytoskeletal injury that was significantly less pronounced in choroidal ECs from young normal monkey eyes. We further show that ECs from AMD eyes are significantly stiffer than their younger counterparts and exhibit peripheral actin organization that is distinct from the longitudinal stress fibers in young ECs. Finally, these differences in complement susceptibility and mechanostructural properties were found to be regulated by the differential activity of the small GTPases Rac and Rho, because Rac inhibition in AMD cells led to simultaneous reduction in stiffness and complement susceptibility, while Rho inhibition in young cells exacerbated complement injury. Thus, by identifying cell stiffness and cytoskeletal regulators Rac and Rho as important determinants of complement susceptibility, the current findings offer a new mechanistic insight into choroidal vascular loss in early AMD that warrants further investigation for assessment of translational potential. © 2022 The Pathological Society of Great Britain and Ireland.

Indexed as

Endothelial CellsMacular DegenerationActinsAgedChoroidComplement Membrane Attack ComplexHumansActinsComplement Membrane Attack Complexactinage-related macular degenerationchoroidcomplement activationendothelial cellsmechanotransductionRacRhostiffness

Identifiers

PMID35239183
PMCPMC9337711
OpenAlexW4214851330

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.