Evidence map›Paper›PMID 26847702›Full record

ArticleScientific reports2016

Impairing autophagy in retinal pigment epithelium leads to inflammasome activation and enhanced macrophage-mediated angiogenesis.

Jian Liu, David A Copland, Sofia Theodoropoulou, Hsi An Amy Chiu, Miriam Durazo Barba, Ka Wang Mak, Matthias Mack, Lindsay B Nicholson, Andrew D Dick

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

Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed, 1 pooled it
7.3field-weighted citation impact, top 3% 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

47 citing papers in PubMed, 1 synthesis or guideline pooled it, 96 citations in OpenAlex.

  1. Pooled it
  2. Autophagy in ocular diseases: from mechanisms to therapeutic potential.Frontiers in cell and developmental biology · 2026
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  17. Article
  18. Article
  19. Protective effects ofJournal of ginseng research · 2023
    Article
  20. Review
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

9 authors at 2 institutions in 2 countries.

Jian LiuSchool of Clinical Sciences, University of Bristol, Bristol, UK.
David A CoplandSchool of Clinical Sciences, University of Bristol, Bristol, UK.
Sofia TheodoropoulouSchool of Clinical Sciences, University of Bristol, Bristol, UK.
Hsi An Amy ChiuSchool of Clinical Sciences, University of Bristol, Bristol, UK.
Miriam Durazo BarbaSchool of Clinical Sciences, University of Bristol, Bristol, UK.
Ka Wang MakSchool of Clinical Sciences, University of Bristol, Bristol, UK.
Matthias MackDepartment of Internal Medicine II, University Hospital Regensburg, Regensburg, Germany.
Lindsay B NicholsonSchool of Clinical Sciences, University of Bristol, Bristol, UK.
Andrew D DickSchool of Clinical Sciences, University of Bristol, Bristol, UK.
University of Bristol · GBUniversity Hospital Regensburg · DE

Funding

The Dunhill Medical Trust R138/1109
6 · The paper itself

Abstract

Age-related decreases in autophagy contribute to the progression of age-related macular degeneration (AMD). We have now studied the interaction between autophagy impaired in retinal pigment epithelium (RPE) and the responses of macrophages. We find that dying RPE cells can activate the macrophage inflammasome and promote angiogenesis. In vitro, inhibiting rotenone-induced autophagy in RPE cells elicits caspase-3 mediated cell death. Co-culture of damaged RPE with macrophages leads to the secretion of IL-1β, IL-6 and nitrite oxide. Exogenous IL-6 protects the dysfunctional RPE but IL-1β causes enhanced cell death. Furthermore, IL-1β toxicity is more pronounced in dysfunctional RPE cells showing reduced IRAK3 gene expression. Co-culture of macrophages with damaged RPE also elicits elevated levels of pro-angiogenic proteins that promote ex vivo choroidal vessel sprouting. In vivo, impaired autophagy in the eye promotes photoreceptor and RPE degeneration and recruitment of inflammasome-activated macrophages. The degenerative tissue environment drives an enhanced pro-angiogenic response, demonstrated by increased size of laser-induced choroidal neovascularization (CNV) lesions. The contribution of macrophages was confirmed by depletion of CCR2(+) monocytes, which attenuates CNV in the presence of RPE degeneration. Our results suggest that the interplay between perturbed RPE homeostasis and activated macrophages influences key features of AMD development.

Indexed as

AnimalsAutophagyCaspase 3Cells, CulturedChoroidal NeovascularizationCoculture TechniquesInflammasomesMacrophagesMacular DegenerationMiceRetinal Pigment EpitheliumRotenoneCaspase 3InflammasomesRotenone

Identifiers

PMID26847702
PMCPMC4742917
OpenAlexW2303528609

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.