Evidence map›Paper›PMID 28632844›Full record

ArticleInvestigative ophthalmology & visual science2017

Complement-Mediated Regulation of Apolipoprotein E in Cultured Human RPE Cells.

Ping Yang, Nikolai P Skiba, Grace M Tewkesbury, Victoria M Treboschi, Peter Baciu, Glenn J Jaffe

Open access · goldAbstract read
In one paragraph

Article in Investigative ophthalmology & visual science, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.8field-weighted citation impact, top 10% 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

18 citing papers in PubMed, 30 citations in OpenAlex.

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  13. Risuteganib Protects against Hydroquinone-induced Injury in Human RPE Cells.Investigative ophthalmology & visual science · 2020
    Article
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  18. Targeting Lipid Metabolism for the Treatment of Age-Related Macular Degeneration: Insights from Preclinical Mouse Models.Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics
    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

6 authors at 2 institutions in 1 country.

Ping YangDepartment of Ophthalmology, Duke University Medical Center, Durham, North Carolina, United States.
Nikolai P SkibaDepartment of Ophthalmology, Duke University Medical Center, Durham, North Carolina, United States.
Grace M TewkesburyDepartment of Ophthalmology, Duke University Medical Center, Durham, North Carolina, United States.
Victoria M TreboschiDepartment of Ophthalmology, Duke University Medical Center, Durham, North Carolina, United States.
Peter BaciuDepartment of Biology, Allergan, Inc., Irvine, California, United States.
Glenn J JaffeDepartment of Ophthalmology, Duke University Medical Center, Durham, North Carolina, United States.
Duke Medical Center · USAllergan (United States) · US

Funding

VISION RESEARCHP30EY005722 · NEI · DUKE UNIVERSITY · PI Vadim Y Arshavsky · 1985 to 2026
$19.3M
NEI NIH HHS P30 EY005722
6 · The paper itself

Abstract

purposeComplement activation is implicated in the pathogenesis of age-related macular degeneration (AMD). Apolipoprotein E (ApoE) and complement activation products such as membrane attack complex (MAC) are present in eyes of individuals with AMD. Herein, we investigated the effect of complement activation on induction of ApoE accumulation in human retinal pigment epithelial (RPE) cells.

methodsCultured human RPE cells were primed with a complement-fixing antibody followed by treatment with C1q-depleted (C1q-Dep) human serum to elicit alternative pathway complement activation. Controls included anti-C5 antibody-treated serum and heat-inactivated C1q-Dep. Total protein was determined on RPE cell extracts, conditioned media, and extracellular matrix (ECM) by Western blot. ApoE and MAC colocalization was assessed on cultured RPE cells and human eyes by immunofluorescent stain. ApoE mRNA expression was evaluated by quantitative PCR (qPCR).

resultsComplement challenge upregulated cell-associated ApoE, but not apolipoprotein A1. ApoE accumulation was blocked by anti-C5 antibody and enhanced by repetitive complement challenge. ApoE mRNA levels were not affected by complement challenge. ApoE was frequently colocalized with MAC in complement-treated cells and drusen from human eyes. ApoE was released into complement-treated conditioned media after a single complement challenge and accumulated on ECM after repetitive complement challenge.

conclusionsComplement challenge induces time-dependent ApoE accumulation in RPE cells. An understanding of the mechanisms by which complement affects RPE ApoE accumulation may help to better explain drusen composition, and provide insights into potential therapeutic targets.

Indexed as

Gene Expression RegulationApolipoproteins EBlotting, WesternCells, CulturedComplement ActivationHumansMacular DegenerationMass SpectrometryMiddle AgedReal-Time Polymerase Chain ReactionRetinal Pigment EpitheliumRNAApolipoproteins ERNA

Identifiers

PMID28632844
PMCPMC5482245
OpenAlexW2646575187

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.