Evidence map›Paper›PMID 26978795›Full record

ArticleeLife2016

Hypoxia-induced metabolic stress in retinal pigment epithelial cells is sufficient to induce photoreceptor degeneration.

Toshihide Kurihara, Peter D Westenskow, Marin L Gantner, Yoshihiko Usui, Andrew Schultz, Stephen Bravo, Edith Aguilar, Carli Wittgrove, Mollie Sh Friedlander, Liliana P Paris and 3 more

Open access · goldAbstract read
In one paragraph

Article in eLife, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 149 papers.

0numbers the graph read from it
0cells of the map it votes in
149citing papers in PubMed
20.4field-weighted citation impact, top 1% 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

149 citing papers in PubMed, 215 citations in OpenAlex.

  1. Trial
  2. Multimodal evaluation of choroidal vascular alterations after panretinal photocoagulation in diabetic retinopathy.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2026
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  10. Mapping the Hypoxic Fitness Landscape of Retinal Pigment Epithelial Cells.International journal of molecular sciences · 2026
    Article
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  13. Selective deletion ofiScience · 2026
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89 more citing papers are in PubMed but not listed here.

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

13 authors at 3 institutions in 1 country.

Toshihide KuriharaDepartment of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, United States.
Peter D WestenskowDepartment of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, United States.
Marin L GantnerThe Lowy Medical Research Institute, La Jolla, United States.
Yoshihiko UsuiDepartment of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, United States.
Andrew SchultzCenter for Metabolomics, The Scripps Research Institute, La Jolla, United States.
Stephen BravoDepartment of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, United States.
Edith AguilarDepartment of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, United States.
Carli WittgroveDepartment of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, United States.
Mollie Sh FriedlanderDepartment of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, United States.
Liliana P ParisDepartment of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, United States.
Emily ChewNational Eye Institute, National Institutes of Health, Bethesda, United States.
Gary SiuzdakCenter for Metabolomics, The Scripps Research Institute, La Jolla, United States.
Martin FriedlanderDepartment of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, United States.ORCID 0000-0003-4238-9651
Scripps Research Institute · USNational Institutes of Health · USThe Lowy Medical Research Institute · US

Funding

INTEGRINS AND OCULAR ANGIOGENESISR01EY011254 · NEI · SCRIPPS RESEARCH INSTITUTE, THE · PI FRIEDLANDER, MARTIN · 1996 to 2016
$11.5M
Age-Related Eye Disease Follow-up Study (AREDS) Follow-up StudyZIAEY000489 · NEI · NATIONAL EYE INSTITUTE · PI CHEW, EMILY Y · 2009 to 2025
$639k
Recapitulating developmental pathways to improve iPSC-RPE derivation protocolsF32EY021416 · NEI · SCRIPPS RESEARCH INSTITUTE, THE · PI WESTENSKOW, PETER DWAYNE · 2011 to 2013
$148k
NEI NIH HHS F32 EY021416NEI NIH HHS R01 EY011254
6 · The paper itself

Abstract

Photoreceptors are the most numerous and metabolically demanding cells in the retina. Their primary nutrient source is the choriocapillaris, and both the choriocapillaris and photoreceptors require trophic and functional support from retinal pigment epithelium (RPE) cells. Defects in RPE, photoreceptors, and the choriocapillaris are characteristic of age-related macular degeneration (AMD), a common vision-threatening disease. RPE dysfunction or death is a primary event in AMD, but the combination(s) of cellular stresses that affect the function and survival of RPE are incompletely understood. Here, using mouse models in which hypoxia can be genetically triggered in RPE, we show that hypoxia-induced metabolic stress alone leads to photoreceptor atrophy. Glucose and lipid metabolism are radically altered in hypoxic RPE cells; these changes impact nutrient availability for the sensory retina and promote progressive photoreceptor degeneration. Understanding the molecular pathways that control these responses may provide important clues about AMD pathogenesis and inform future therapies.

Indexed as

HypoxiaStress, PhysiologicalAnimalsDisease Models, AnimalEpithelial CellsMacular DegenerationMicePhotoreceptor CellsRetinal Pigment Epitheliumage-related macular degenerationcell biologyhypoxiamouseneuroscienceneurovascular crosstalk

Identifiers

PMID26978795
PMCPMC4848091
OpenAlexW2327580634

What OpenQuestion holds

Textmetadata
LicenceCC0
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.