Evidence map›Paper›PMID 29269042›Full record

ArticleEBioMedicine2018

HtrA1 Mediated Intracellular Effects on Tubulin Using a Polarized RPE Disease Model.

Esther Melo, Philipp Oertle, Carolyn Trepp, Hélène Meistermann, Thomas Burgoyne, Lorenzo Sborgi, Alvaro Cortes Cabrera, Chia-Yi Chen, Jean-Christophe Hoflack, Tony Kam-Thong and 21 more

Open access · goldAbstract read
In one paragraph

Article in EBioMedicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.6field-weighted citation impact, top 16% 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

13 citing papers in PubMed, 20 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

31 authors at 5 institutions in 3 countries.

Esther MeloRoche Pharma Research & Early Development, Roche Innovation Center Basel, Basel 4070, Switzerland. Electronic address: esther.melo@roche.com.
Philipp OertleBiozentrum and the Swiss Nanoscience Institute, University of Basel, Basel 4056, Switzerland.
Carolyn TreppDepartment of Ophthalmology, Department of Clinical Research, Inselspital, Bern University Hospital, University of Bern, Bern 3010, Switzerland.
Hélène MeistermannRoche Pharma Research & Early Development, Roche Innovation Center Basel, Basel 4070, Switzerland.
Thomas BurgoyneInstitute of Ophthalmology, University College London, London EC1V9EL, United Kingdom.
Lorenzo SborgiBiozentrum and the Swiss Nanoscience Institute, University of Basel, Basel 4056, Switzerland.
Alvaro Cortes CabreraRoche Pharma Research & Early Development, Roche Innovation Center Basel, Basel 4070, Switzerland.
Chia-Yi ChenInstitute of Molecular Medicine and Cell Research, University of Freiburg, Freiburg D-79104, Germany.
Jean-Christophe HoflackRoche Pharma Research & Early Development, Roche Innovation Center Basel, Basel 4070, Switzerland.
Tony Kam-ThongRoche Pharma Research & Early Development, Roche Innovation Center Basel, Basel 4070, Switzerland.
Roland SchmuckiRoche Pharma Research & Early Development, Roche Innovation Center Basel, Basel 4070, Switzerland.
Laura BadiRoche Pharma Research & Early Development, Roche Innovation Center Basel, Basel 4070, Switzerland.
Nicholas FlintRoche Pharma Research & Early Development, Roche Innovation Center Basel, Basel 4070, Switzerland.
Zeynep Eren GhianiRoche Pharma Research & Early Development, Roche Innovation Center Basel, Basel 4070, Switzerland.
Fréderic DelobelRoche Pharma Research & Early Development, Roche Innovation Center Basel, Basel 4070, Switzerland.
Corinne StuckiRoche Pharma Research & Early Development, Roche Innovation Center Basel, Basel 4070, Switzerland.
Giulia GromoRoche Pharma Research & Early Development, Roche Innovation Center Basel, Basel 4070, Switzerland.
Alfred EinhausRoche Pharma Research & Early Development, Roche Innovation Center Basel, Basel 4070, Switzerland.
Benoit HornspergerRoche Pharma Research & Early Development, Roche Innovation Center Basel, Basel 4070, Switzerland.
Sabrina GollingRoche Pharma Research & Early Development, Roche Innovation Center Basel, Basel 4070, Switzerland.
Juliane Siebourg-PolsterRoche Pharma Research & Early Development, Roche Innovation Center Basel, Basel 4070, Switzerland.
Francoise GerberRoche Pharma Research & Early Development, Roche Innovation Center Basel, Basel 4070, Switzerland.
Bernd BohrmannRoche Pharma Research & Early Development, Roche Innovation Center Basel, Basel 4070, Switzerland.
Clare FutterInstitute of Ophthalmology, University College London, London EC1V9EL, United Kingdom.
Tom DunkleyRoche Pharma Research & Early Development, Roche Innovation Center Basel, Basel 4070, Switzerland.
Sebastian HillerBiozentrum and the Swiss Nanoscience Institute, University of Basel, Basel 4056, Switzerland.
Oliver SchillingInstitute of Molecular Medicine and Cell Research, University of Freiburg, Freiburg D-79104, Germany; BIOSS Centre for Biological Signaling Studies, University of Freiburg, Freiburg D-79104, Germany.
Volker EnzmannDepartment of Ophthalmology, Department of Clinical Research, Inselspital, Bern University Hospital, University of Bern, Bern 3010, Switzerland.
Sascha FauserRoche Pharma Research & Early Development, Roche Innovation Center Basel, Basel 4070, Switzerland.
Marija PlodinecBiozentrum and the Swiss Nanoscience Institute, University of Basel, Basel 4056, Switzerland. Electronic address: marija.plodinec@unibas.ch.
Roberto IaconeRoche Pharma Research & Early Development, Roche Innovation Center Basel, Basel 4070, Switzerland. Electronic address: roberto.iacone47@gmail.com.
Roche (Switzerland) · CHUniversity of Basel · CHUniversity College London · GBUniversity of Bern · CHUniversity of Freiburg · DE

Funding

Medical Research Council MR/P010091/1
6 · The paper itself

Abstract

Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss. The protein HtrA1 is enriched in retinal pigment epithelial (RPE) cells isolated from AMD patients and in drusen deposits. However, it is poorly understood how increased levels of HtrA1 affect the physiological function of the RPE at the intracellular level. Here, we developed hfRPE (human fetal retinal pigment epithelial) cell culture model where cells fully differentiated into a polarized functional monolayer. In this model, we fine-tuned the cellular levels of HtrA1 by targeted overexpression. Our data show that HtrA1 enzymatic activity leads to intracellular degradation of tubulin with a corresponding reduction in the number of microtubules, and consequently to an altered mechanical cell phenotype. HtrA1 overexpression further leads to impaired apical processes and decreased phagocytosis, an essential function for photoreceptor survival. These cellular alterations correlate with the AMD phenotype and thus highlight HtrA1 as an intracellular target for therapeutic interventions towards AMD treatment.

Indexed as

Cell PolarityModels, BiologicalAdherens JunctionsAdultFetusHigh-Temperature Requirement A Serine Peptidase 1HumansMacular DegenerationMicrotubulesMutationNanoparticlesPhagocytosisPolymerizationProtein AggregatesProtein BindingRetinal Pigment EpitheliumHigh-Temperature Requirement A Serine Peptidase 1Protein AggregatesTubulinAge-related macular degenerationCell stiffnessDisease modellingHtrA serine peptidase 1Mechanical propertiesPhagocytic activityPolarized human retinal, pigmented epithelium

Identifiers

PMID29269042
PMCPMC5828370
OpenAlexW2771157869

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.