Evidence map›Paper›PMID 34643794›Full record

ArticleGraefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie2022

Pro-inflammatory activation changes intracellular transport of bevacizumab in the retinal pigment epithelium in vitro.

Julia Hildebrandt, Tom Käckenmeister, Katrin Winkelmann, Philipp Dörschmann, Johann Roider, Alexa Klettner

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

Article in Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.6field-weighted citation impact, top 35% 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

2 citing papers in PubMed, 4 citations in OpenAlex.

  1. Article
  2. 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

6 authors at 1 institution in 1 country.

Julia HildebrandtDepartment of Ophthalmology, University Medical Center, University of Kiel, Quincke Research Center, Rosalind-Franklin-Str. 9, 24105, Kiel, Germany.
Tom KäckenmeisterDepartment of Ophthalmology, University Medical Center, University of Kiel, Quincke Research Center, Rosalind-Franklin-Str. 9, 24105, Kiel, Germany.
Katrin WinkelmannDepartment of Ophthalmology, University Medical Center, University of Kiel, Quincke Research Center, Rosalind-Franklin-Str. 9, 24105, Kiel, Germany.
Philipp DörschmannDepartment of Ophthalmology, University Medical Center, University of Kiel, Quincke Research Center, Rosalind-Franklin-Str. 9, 24105, Kiel, Germany.
Johann RoiderDepartment of Ophthalmology, University Medical Center, University of Kiel, Quincke Research Center, Rosalind-Franklin-Str. 9, 24105, Kiel, Germany.
Alexa KlettnerDepartment of Ophthalmology, University Medical Center, University of Kiel, Quincke Research Center, Rosalind-Franklin-Str. 9, 24105, Kiel, Germany. AlexaKarina.Klettner@uksh.de.ORCID http://orcid.org/0000-0002-2709-1059
Christian-Albrechts-Universität zu Kiel · DE

Funding

Dr. Werner Jackstädt-Stiftung (DE) 19/07/2016Stifterverband H17057015020215353
6 · The paper itself

Abstract

purposeBevacizumab is taken up and transported through the retinal pigment epithelium. Inflammatory signaling may influence this interaction. In the present study, we have investigated the effect of pro-inflammatory stimuli on the uptake, intracellular localization, and transepithelial transport of bevacizumab.

methodsARPE-19 cell line or primary porcine RPE cells were treated with clinical relevant concentrations of bevacizumab (250 µg/ml). Pro-inflammatory signaling was induced by TLR-3 agonist polyinosinic:polycytidylic acid (Poly I:C). Viability was investigated with MTT and trypan-blue exclusion assay, and cell number, uptake, and intracellular localization were investigated with immunofluorescence, investigating also actin filaments, the motor protein myosin 7a and lysosomes. Immunofluorescence signals were quantified. Intracellular bevacizumab was additionally detected in Western blot. Barrier function was investigated with transepithelial resistant measurements (TER). The transepithelial transport of bevacizumab and its influence on cytokine (IL-6, IL-8, IL-1β, TNFα) secretion was investigated with ELISA.

resultsPoly I:C in combination with bevacizumab reduced the viability of the cells. Treatment with Poly I:C reduced the uptake of bevacizumab, changed the intensity of the actin filaments, and reduced the colocalization with myosin 7a. In addition, Poly I:C reduced the capacity of RPE cells to transport bevacizumab over the barrier. In addition, bevacizumab reduced the secretion of IL-8 and TNFα after Poly I:C stimulation at selected time points.

conclusionsPro-inflammatory activation of RPE cells with TLR-3 agonist Poly I:C changes the interaction of RPE cells with the anti-VEGF compound bevacizumab, reducing its uptake and transport. On the other hand, bevacizumab might influence pro-inflammatory cytokine release. Our data indicate that inflammation may influence the pharmacokinetic of bevacizumab in the retina.

Indexed as

Angiogenesis InhibitorsRetinal Pigment EpitheliumAnimalsBevacizumabBlotting, WesternCells, CulturedSwineAngiogenesis InhibitorsBevacizumabActin filamentsBevacizumabMyosin 7aRetinal pigment epithelium (RPE)Toll-like receptor (TLR-3)Transepithelial transport

Identifiers

PMID34643794
PMCPMC8850249
OpenAlexW3205188604

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.