Evidence map›Paper›PMID 30997640›Full record

ArticleMolecular neurobiology2019

Sphingosine Kinase-1 Is Essential for Maintaining External/Outer Limiting Membrane and Associated Adherens Junctions in the Aging Retina.

Joseph L Wilkerson, Megan A Stiles, Jami M Gurley, Richard C Grambergs, Xiaowu Gu, Michael H Elliott, Richard L Proia, Nawajes A Mandal

Abstract read
In one paragraph

Article in Molecular neurobiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed, 1 pooled it
0.8field-weighted citation impact, top 29% 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

7 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.

  1. Differential diagnosis of myopic choroidal neovascularization (mCNV): insights from multimodal imaging and treatment implications.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2024
    Pooled it
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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

8 authors at 3 institutions in 1 country.

Joseph L WilkersonDepartment of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA.
Megan A StilesDean A. McGee Eye Institute, Oklahoma City, OK, 73104, USA.
Jami M GurleyDean A. McGee Eye Institute, Oklahoma City, OK, 73104, USA.
Richard C GrambergsDepartment of Ophthalmology and Anatomy and Neurobiology, University of Tennessee Health Sciences Center, Memphis, TN, 38163, USA.
Xiaowu GuDean A. McGee Eye Institute, Oklahoma City, OK, 73104, USA.
Michael H ElliottDean A. McGee Eye Institute, Oklahoma City, OK, 73104, USA.
Richard L ProiaGenetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
Nawajes A MandalDepartment of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA. nmandal@uthsc.edu.ORCID http://orcid.org/0000-0003-4489-7748
Dean McGee Eye Institute · USUniversity of Tennessee Health Science Center · USNational Institutes of Health · US

Funding

Virus Vector Shared ResourceP30CA016059 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI Kim Felder Rhoads · 1985 to 2026
$51.0M
Sphingolipid Biology of NeurodegenerationZIADK056016 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI PROIA, RICHARD · 2009 to 2025
$21.3M
Mouse Models of Novel Sphingolipid Biology and Disease MechanismsZIADK056014 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI PROIA, RICHARD · 2009 to 2025
$10.6M
P30-CENTER CORE GRANT FOR VISION RESEARCHP30EY021725 · NEI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI Michelle C Callegan, MICHAEL H ELLIOTT · 2011 to 2026
$10.5M
Sphingolipid Metabolism and Signaling in the RetinaR01EY022071 · NEI · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · PI MANDAL, NAWAJES · 2012 to 2016
$1.8M
Vision Science Training ProgramT32EY023202 · NEI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI CALLEGAN, MICHELLE C · 2014 to 2025
$952k
Sphingolipid signaling in corneal wound healing and fibrosisR21EY025256 · NEI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI KARAMICHOS, DIMITRIOS, MANDAL, NAWAJES · 2015 to 2016
$429k
NCI NIH HHS P30 CA016059NEI NIH HHS EY022071NEI NIH HHS EY025256NEI NIH HHS P30 EY021725NEI NIH HHS R01 EY022071NEI NIH HHS R21 EY025256NEI NIH HHS T32 EY023202NIH HHS T32EY023202
6 · The paper itself

Abstract

Sphingosine-1-phosphate (S1P) produced by sphingosine kinases (SPHK1 and SPHK2) is a signaling molecule involved in cell proliferation and formation of cellular junctions. In this study, we characterized the retinas of Sphk1 knockout (KO) mice by electron microscopy and immunocytochemistry. We also tested cultured Müller glia for their response to S1P. We found that S1P plays an important role in retinal and retinal pigment epithelial (RPE) structural integrity in aging mice. Ultrastructural analysis of Sphk1 KO mouse retinas aged to 15 months or raised with moderate light stress revealed a degenerated outer limiting membrane (OLM). This membrane is formed by adherens junctions between neighboring Müller glia and photoreceptor cells. We also show that Sphk1 KO mice have reduced retinal function in mice raised with moderate light stress. In vitro assays revealed that exogenous S1P modulated cytoskeletal rearrangement and increased N-cadherin production in human Müller glia cells. Aged mice also had morphological degeneration of the RPE, as well as increased lipid storage vacuoles and undigested phagosomes reminiscent of RPE in age-related macular degeneration. These findings show that SPHK1 and S1P play a vital role in the structural maintenance of the mammalian retina and retinal pigmented epithelium by supporting the formation of adherens junctions.

Indexed as

Adherens JunctionsAgingAnimalsCadherinscdc42 GTP-Binding ProteinCell MembraneEndotheliumEpendymoglial CellsHumansLysophospholipidsMice, KnockoutPhenotypePhosphotransferases (Alcohol Group Acceptor)rac1 GTP-Binding ProteinRetinaRetinal Pigment EpitheliumCadherinscdc42 GTP-Binding ProteinLysophospholipidsPhosphotransferases (Alcohol Group Acceptor)rac1 GTP-Binding ProteinSphingolipidsSphingosinesphingosine 1-phosphateSphingosine KinaseN-cadherinOuter limiting membraneRetinaRetinal degenerationSphingosine-1-phosphateSphingosine kinase

Identifiers

PMID30997640
PMCPMC7425817
OpenAlexW2938112976

What OpenQuestion holds

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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.