Evidence map›Paper›PMID 26187344›Full record

ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2015

Serum levels of lipid metabolites in age-related macular degeneration.

Tivadar Orban, William M Johnson, Zhiqian Dong, Tadao Maeda, Akiko Maeda, Tsutomu Sakai, Hiroshi Tsuneoka, John J Mieyal, Krzysztof Palczewski

Abstract readClinical Study
PubMed Full text at PMC Publisher
In one paragraph

Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
2.6field-weighted citation impact, top 12% 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

16 citing papers in PubMed, 29 citations in OpenAlex.

  1. Review
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  9. Review
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  13. Article
  14. Lipids, oxidized lipids, oxidation-specific epitopes, and Age-related Macular Degeneration.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2017
    Review
  15. Article
  16. 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 3 institutions in 2 countries.

Tivadar Orban*Department of Pharmacology and Department of Ophthalmology and Visual Sciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA; Polgenix, Incorporated, Cleveland, Ohio, USA; Department of Ophthalmology, Jikei University School of Medicine, Tokyo, Japan; and Louis Stokes Veterans Affairs Medical Research Center, Cleveland, Ohio, USA.
William M Johnson*Department of Pharmacology and Department of Ophthalmology and Visual Sciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA; Polgenix, Incorporated, Cleveland, Ohio, USA; Department of Ophthalmology, Jikei University School of Medicine, Tokyo, Japan; and Louis Stokes Veterans Affairs Medical Research Center, Cleveland, Ohio, USA.
Zhiqian Dong*Department of Pharmacology and Department of Ophthalmology and Visual Sciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA; Polgenix, Incorporated, Cleveland, Ohio, USA; Department of Ophthalmology, Jikei University School of Medicine, Tokyo, Japan; and Louis Stokes Veterans Affairs Medical Research Center, Cleveland, Ohio, USA.
Tadao Maeda*Department of Pharmacology and Department of Ophthalmology and Visual Sciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA; Polgenix, Incorporated, Cleveland, Ohio, USA; Department of Ophthalmology, Jikei University School of Medicine, Tokyo, Japan; and Louis Stokes Veterans Affairs Medical Research Center, Cleveland, Ohio, USA.
Akiko Maeda*Department of Pharmacology and Department of Ophthalmology and Visual Sciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA; Polgenix, Incorporated, Cleveland, Ohio, USA; Department of Ophthalmology, Jikei University School of Medicine, Tokyo, Japan; and Louis Stokes Veterans Affairs Medical Research Center, Cleveland, Ohio, USA.
Tsutomu Sakai*Department of Pharmacology and Department of Ophthalmology and Visual Sciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA; Polgenix, Incorporated, Cleveland, Ohio, USA; Department of Ophthalmology, Jikei University School of Medicine, Tokyo, Japan; and Louis Stokes Veterans Affairs Medical Research Center, Cleveland, Ohio, USA.
Hiroshi Tsuneoka*Department of Pharmacology and Department of Ophthalmology and Visual Sciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA; Polgenix, Incorporated, Cleveland, Ohio, USA; Department of Ophthalmology, Jikei University School of Medicine, Tokyo, Japan; and Louis Stokes Veterans Affairs Medical Research Center, Cleveland, Ohio, USA.
John J Mieyal*Department of Pharmacology and Department of Ophthalmology and Visual Sciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA; Polgenix, Incorporated, Cleveland, Ohio, USA; Department of Ophthalmology, Jikei University School of Medicine, Tokyo, Japan; and Louis Stokes Veterans Affairs Medical Research Center, Cleveland, Ohio, USA.
Krzysztof Palczewski*Department of Pharmacology and Department of Ophthalmology and Visual Sciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA; Polgenix, Incorporated, Cleveland, Ohio, USA; Department of Ophthalmology, Jikei University School of Medicine, Tokyo, Japan; and Louis Stokes Veterans Affairs Medical Research Center, Cleveland, Ohio, USA kxp65@case.edu.
Case Western Reserve University · USJikei University School of Medicine · JPPolgenix (United States) · US

Funding

STRUCTURAL STUDIES OF ARRESTINSR01EY009339 · NEI · UNIVERSITY OF WASHINGTON · PI KISER, PHILIP DAVID, PALCZEWSKI, KRZYSZTOF · 1992 to 2025
$16.0M
Pharmacological Treatment of Retinal DiseasesR24EY021126 · NEI · CASE WESTERN RESERVE UNIVERSITY · PI PALCZEWSKI, KRZYSZTOF · 2010 to 2014
$12.8M
PREDOCTORAL TRAINING PROGRAM IN MOLECULAR THERAPEUTICST32GM008803 · NIGMS · CASE WESTERN RESERVE UNIVERSITY · PI MIEYAL, JOHN J, NIEMAN, MARVIN THOMAS · 2001 to 2023
$4.2M
NEI NIH HHS EY009339NEI NIH HHS EY021126NEI NIH HHS R01 EY009339NEI NIH HHS R24 EY021126NIGMS NIH HHS T32 GM008803
6 · The paper itself

Abstract

Age-related macular degeneration (AMD) is a neurodegenerative disease that causes adult-onset blindness. There are 2 forms of this progressive disease: wet and dry. Currently there is no cure for AMD, but several treatment options have started to emerge making early detection critical for therapeutic success. Analysis of the eyes of Abca4(-/-)Rdh8(-/-) mice that display light-induced retinal degeneration indicates that 11-cis-retinal and docosahexaenoic acid (DHA) levels were significantly decreased as compared with the eyes of control dark-adapted C57BL/6J mice. In addition, exposure to intense light correlated with higher levels of prostaglandin G2 in the eyes of Abca4(-/-)Rdh8(-/-) mice. Intense light exposure also lowered DHA levels in the eyes of wild-type C57BL/6J mice without discernible retinal degeneration. Analysis of human serum from patients with AMD recapitulated these dysregulated DHA levels and revealed dysregulation of arachidonic acid (AA) levels as well (∼32% increase in patients with AMD compared with average levels in healthy individuals). From these observations, we then built a statistical model that included levels of DHA and AA from human serum. This model had a 74% probability of correctly identifying patients with AMD from controls. Addition of a genetic analysis for one of the most prevalent amino acid substitutions in the age-related maculopathy susceptibility 2 gene linked to AMD, Ala(69)→Ser, did not improve the statistical model. Thus, we have characterized a reliable method with the potential to detect AMD without a genetic component, paving the way for a larger-scale clinical evaluation. Our studies on mouse models along with the analysis of human serum suggest that our small molecule-based model may serve as an effective tool to estimate the risk of developing AMD.

Indexed as

Models, BiologicalAdultAgedAlcohol OxidoreductasesAmino Acid SubstitutionAnimalsATP-Binding Cassette TransportersDocosahexaenoic AcidsFemaleHumansMacular DegenerationMaleMiceMice, KnockoutMiddle AgedMutation, MissenseAbca4 protein, mouseAlcohol OxidoreductasesATP-Binding Cassette TransportersDocosahexaenoic AcidsHSD17B6 protein, mouseRetinaldehydearachidonic aciddocosahexaenoic acidmouse modelrisk evaluationserum

Identifiers

PMID26187344
PMCPMC4608905
OpenAlexW1649634111

What OpenQuestion holds

Textmetadata
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.