Evidence map›Paper›PMID 34221496›Full record

ArticleJournal of ophthalmology2021

Human Platelets Take up Anti-VEGF Agents.

B Sobolewska, B Fehrenbacher, P Münzer, H Kalbacher, S Geue, Konstantinos Stellos, M Schaller, F Ziemssen

Open access · goldAbstract read
In one paragraph

Article in Journal of ophthalmology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.4field-weighted citation impact, top 38% 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

3 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Article
  3. 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

8 authors at 2 institutions in 2 countries.

B SobolewskaCenter for Ophthalmology, Eberhard Karls University Tuebingen, Tuebingen, Germany.ORCID https://orcid.org/0000-0001-8643-6873
B FehrenbacherDepartment of Dermatology, Eberhard Karls University Tuebingen, Tuebingen, Germany.
P MünzerDepartment of Cardiology and Cardiovascular Medicine, University of Tuebingen, Tuebingen, Germany.
H KalbacherInterfaculty Institute of Biochemistry, Eberhard Karls University Tuebingen, Tuebingen, Germany.
S GeueDepartment of Cardiology and Cardiovascular Medicine, University of Tuebingen, Tuebingen, Germany.
Konstantinos StellosBiosciences Institute, Vascular Biology and Medicine Theme, Newcastle University, Newcastle upon Tyne, UK.
M SchallerDepartment of Dermatology, Eberhard Karls University Tuebingen, Tuebingen, Germany.
F ZiemssenCenter for Ophthalmology, Eberhard Karls University Tuebingen, Tuebingen, Germany.ORCID https://orcid.org/0000-0002-3873-0581
University of Tübingen · DENewcastle upon Tyne Hospitals NHS Foundation Trust · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeGrowing evidence suggests different systemic exposure of anti-vascular endothelial growth factor (anti-VEGF) agents with repeated intravitreal application. Since the penetration of anti-VEGF agents through vascular barrier was reported, the interaction of anti-VEGF with nonresident platelets has become a topic of interest. The purpose of this study was to evaluate, with the help of visualization techniques, whether platelets take up the anti-VEGF agents ranibizumab, aflibercept, and bevacizumab.

methodsThe uptake of anti-VEGF agents with or without VEGF treatment was investigated using immunofluorescence and immunogold staining in human platelets. The role of actin filaments and clathrin-coated vesicles in the transport of ranibizumab, aflibercept, and bevacizumab was evaluated by two pharmacologic inhibitors: staurosporine (protein kinase C inhibitor) and cytochalasin D.

resultsAll three anti-VEGF agents were taken up by platelets and colocalized with VEGF. Ranibizumab and aflibercept were mainly detected in alpha-granules; however, bevacizumab was equally localized in alpha-granules and in platelet vesicles. Both staurosporine and cytochalasin D completely inhibited the uptake of aflibercept into platelets. Both pharmacological inhibitors also decreased the transport of ranibizumab and bevacizumab into platelets. Bevacizumab was significantly more frequently colocalized within clathrin-coated vesicles than ranibizumab and aflibercept.

conclusionAll three anti-VEGF agents are taken up by platelets and internalized in alpha-granules, which may result in a higher local exposure of anti-VEGF after the activation of platelets, potentially contributing to arterial thromboembolic events. Clathrin-coated vesicles seem to be more prominent in the transport of bevacizumab than ranibizumab and aflibercept. Nevertheless, whether the different localization and transport of bevacizumab are truly related to specific differences of receptor-mediated endocytosis has to be revealed by further research.

Identifiers

PMID34221496
PMCPMC8219439
OpenAlexW3168217639

What OpenQuestion holds

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Registered trials

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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.