Evidence map›Paper›PMID 31923239›Full record

ArticlePloS one2020

Novel imaging biomarkers for mapping the impact of mild mitochondrial uncoupling in the outer retina in vivo.

Bruce A Berkowitz, Hailey K Olds, Collin Richards, Joydip Joy, Tilman Rosales, Robert H Podolsky, Karen Lins Childers, W Brad Hubbard, Patrick G Sullivan, Shasha Gao and 3 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2020. 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
1.1field-weighted citation impact, top 24% 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, 18 citations in OpenAlex.

  1. Article
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  9. OCT imaging of rod mitochondrial respirationExperimental biology and medicine (Maywood, N.J.) · 2021
    Review
  10. Review
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  14. Rod Photoreceptor Neuroprotection in Dark-Reared Pde6brd10 Mice.Investigative ophthalmology & visual science · 2020
    Article
  15. Review
  16. Article
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 4 institutions in 2 countries.

Bruce A BerkowitzDepartment of Ophthalmology, Visual and Anatomical Sciences, Wayne State University School of Medicine, Detroit, MI, United States of America.ORCID 0000-0003-0291-2209
Hailey K OldsDepartment of Ophthalmology, Visual and Anatomical Sciences, Wayne State University School of Medicine, Detroit, MI, United States of America.
Collin RichardsDepartment of Ophthalmology, Visual and Anatomical Sciences, Wayne State University School of Medicine, Detroit, MI, United States of America.
Joydip JoyDepartment of Ophthalmology, Visual and Anatomical Sciences, Wayne State University School of Medicine, Detroit, MI, United States of America.
Tilman RosalesDepartment of Ophthalmology, Visual and Anatomical Sciences, Wayne State University School of Medicine, Detroit, MI, United States of America.
Robert H PodolskyBeaumont Research Institute, Beaumont Health, Royal Oak, MI, United States of America.ORCID 0000-0003-3547-8859
Karen Lins ChildersBeaumont Research Institute, Beaumont Health, Royal Oak, MI, United States of America.
W Brad HubbardSpinal Cord and Brain Injury Research Center, University of Kentucky, Lexington, KY, United States of America.ORCID 0000-0001-7018-0148
Patrick G SullivanSpinal Cord and Brain Injury Research Center, University of Kentucky, Lexington, KY, United States of America.
Shasha GaoVisual Function Core, National Eye Institute, National Institutes of Health, Bethesda, MD, United States of America.
Yichao LiVisual Function Core, National Eye Institute, National Institutes of Health, Bethesda, MD, United States of America.
Haohua QianVisual Function Core, National Eye Institute, National Institutes of Health, Bethesda, MD, United States of America.
Robin RobertsDepartment of Ophthalmology, Visual and Anatomical Sciences, Wayne State University School of Medicine, Detroit, MI, United States of America.
Wayne State University · USNational Institutes of Health · USBeaumont Health · USUniversity of Kentucky · US

Funding

PROTECTIVE ACTIONS OF ESTRADIOL/SERMS ON BRAIN/HIVP20RR015592 · NCRR · UNIVERSITY OF KENTUCKY · PI CURRY, THOMAS E · 2000 to 2009
$18.2M
VISION RESEARCH--COREP30EY004068 · NEI · WAYNE STATE UNIVERSITY · PI LINDA D HAZLETT · 1985 to 2026
$13.2M
ROLE OF CALCIUM, CALPAINS, AND CASPASES IN NEURODEGENERATIONP01AG010836 · NIA · UNIVERSITY OF KENTUCKY · PI LANDFIELD, PHILIP W. · 1992 to 2008
$12.4M
Visual Function CoreZICEY000503 · NEI · NATIONAL EYE INSTITUTE · PI QIAN, HAOHUA · 2011 to 2025
$12.3M
HIPPOCAMPAL SYNAPTIC STRUCTURE--PHYSIOLOGY DURING AGINGR37AG004542 · NIA · UNIVERSITY OF KENTUCKY · PI LANDFIELD, PHILIP W. · 1998 to 2020
$7.1M
Psychosocial stress interactions with electrophysiology and brain agingR01AG037868 · NIA · UNIVERSITY OF KENTUCKY · PI BLALOCK, ERIC · 2011 to 2025
$3.5M
Metabolic syndrome and hippocampal Ca2+ dysregulation in aging-related memory decR01AG033649 · NIA · UNIVERSITY OF KENTUCKY · PI THIBAULT, OLIVIER · 2009 to 2019
$3.4M
Hippocampal Electrophysiology and Myelinogenesis in Healthy Cognitive AgingR01AG034605 · NIA · UNIVERSITY OF KENTUCKY · PI LANDFIELD, PHILIP W. · 2009 to 2015
$2.9M
Novel Imaging Biomarker for Treating Spatial Memory Loss in Prodromal Alzheimer's Disease ModelsR01AG058171 · NIA · WAYNE STATE UNIVERSITY · PI BENNETT, BRIAN M, BERKOWITZ, BRUCE A. · 2017 to 2021
$2.8M
TRAINING PROGRAM IN OXIDATIVE STRESS AND NUTRITIONT32DK007778 · NIDDK · UNIVERSITY OF KENTUCKY · PI WEBB, NANCY R · 2000 to 2019
$2.5M
Training in Translational Research in Alzheimer's and Related Dementias (TRIAD)T32AG057461 · NIA · UNIVERSITY OF KENTUCKY · PI MURPHY, MICHAEL PAUL, VAN ELDIK, LINDA J · 2017 to 2021
$2.1M
Testing the Calcium Hypothesis of Age-related Cognitive DeclineR01AG052934 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MURPHY, GEOFFREY G · 2016 to 2020
$2.1M
BLRD VA I01 BX003405NCRR NIH HHS P20 RR015592NEI NIH HHS P30 EY004068NEI NIH HHS R01 EY026584NIA NIH HHS P01 AG010836NIA NIH HHS R01 AG020251NIA NIH HHS R01 AG034605NIA NIH HHS R01 AG052934NIA NIH HHS R01 AG058171NIA NIH HHS R21 AG029268NIA NIH HHS R37 AG004542
6 · The paper itself

Abstract

purposeTo test the hypothesis that imaging biomarkers are useful for evaluating in vivo rod photoreceptor cell responses to a mitochondrial protonophore.

methodsIntraperitoneal injections of either the mitochondrial uncoupler 2,4 dinitrophenol (DNP) or saline were given to mice with either higher [129S6/eVTac (S6)] or lower [C57BL/6J (B6)] mitochondrial reserve capacities and were studied in dark or light. We measured: (i) the external limiting membrane-retinal pigment epithelium region thickness (ELM-RPE; OCT), which decreases substantially with upregulation of a pH-sensitive water removal co-transporter on the apical portion of the RPE, and (ii) the outer retina R1 (= 1/(spin lattice relaxation time (T1), an MRI parameter proportional to oxygen / free radical content.

resultsIn darkness, baseline rod energy production and consumption are relatively high compared to that in light, and additional metabolic stimulation with DNP provoked thinning of the ELM-RPE region compared to saline injection in S6 mice; ELM-RPE thickness was unresponsive to DNP in B6 mice. Also, dark-adapted S6 mice given DNP showed a decrease in outer retina R1 values compared to saline injection in the inferior retina. In dark-adapted B6 mice, transretinal R1 values were unresponsive to DNP in superior and inferior regions. In light, with its relatively lower basal rod energy production and consumption, DNP caused ELM-RPE thinning in both S6 and B6 mice.

conclusionsThe present results raise the possibility of non-invasively evaluating the mouse rod mitochondrial energy ecosystem using new DNP-assisted OCT and MRI in vivo assays.

Indexed as

Magnetic Resonance ImagingTomography, Optical CoherenceAdaptation, PhysiologicalAnimalsBiomarkersDarknessMaleMiceMice, Inbred C57BLMitochondriaRetinaBiomarkers

Identifiers

PMID31923239
PMCPMC6953833
OpenAlexW2999330590

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.