Evidence map›Paper›PMID 25667222›Full record

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

Adrenergic and serotonin receptors affect retinal superoxide generation in diabetic mice: relationship to capillary degeneration and permeability.

Yunpeng Du, Megan Cramer, Chieh Allen Lee, Jie Tang, Arivalagan Muthusamy, David A Antonetti, Hui Jin, Krzysztof Palczewski, Timothy S Kern

Open access · bronzeAbstract read
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 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
3.5field-weighted citation impact, top 7% 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

44 citing papers in PubMed, 49 citations in OpenAlex.

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  11. The serotonergic system dysfunction in diabetes mellitus.Frontiers in cellular neuroscience · 2022
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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

9 authors at 3 institutions in 1 country.

Yunpeng Du*Department of Medicine, Case Western Reserve University, Cleveland, Ohio, USA; Department of Ophthalmology and Visual Sciences, The University of Michigan, Ann Arbor, Michigan, USA; Department of Pharmacology, Case Western Reserve University, Cleveland, Ohio, USA; and Veterans Administration Medical Center Research Service 151, Cleveland, Ohio, USA.
Megan Cramer*Department of Medicine, Case Western Reserve University, Cleveland, Ohio, USA; Department of Ophthalmology and Visual Sciences, The University of Michigan, Ann Arbor, Michigan, USA; Department of Pharmacology, Case Western Reserve University, Cleveland, Ohio, USA; and Veterans Administration Medical Center Research Service 151, Cleveland, Ohio, USA.
Chieh Allen Lee*Department of Medicine, Case Western Reserve University, Cleveland, Ohio, USA; Department of Ophthalmology and Visual Sciences, The University of Michigan, Ann Arbor, Michigan, USA; Department of Pharmacology, Case Western Reserve University, Cleveland, Ohio, USA; and Veterans Administration Medical Center Research Service 151, Cleveland, Ohio, USA.
Jie Tang*Department of Medicine, Case Western Reserve University, Cleveland, Ohio, USA; Department of Ophthalmology and Visual Sciences, The University of Michigan, Ann Arbor, Michigan, USA; Department of Pharmacology, Case Western Reserve University, Cleveland, Ohio, USA; and Veterans Administration Medical Center Research Service 151, Cleveland, Ohio, USA.
Arivalagan Muthusamy*Department of Medicine, Case Western Reserve University, Cleveland, Ohio, USA; Department of Ophthalmology and Visual Sciences, The University of Michigan, Ann Arbor, Michigan, USA; Department of Pharmacology, Case Western Reserve University, Cleveland, Ohio, USA; and Veterans Administration Medical Center Research Service 151, Cleveland, Ohio, USA.
David A Antonetti*Department of Medicine, Case Western Reserve University, Cleveland, Ohio, USA; Department of Ophthalmology and Visual Sciences, The University of Michigan, Ann Arbor, Michigan, USA; Department of Pharmacology, Case Western Reserve University, Cleveland, Ohio, USA; and Veterans Administration Medical Center Research Service 151, Cleveland, Ohio, USA.
Hui Jin*Department of Medicine, Case Western Reserve University, Cleveland, Ohio, USA; Department of Ophthalmology and Visual Sciences, The University of Michigan, Ann Arbor, Michigan, USA; Department of Pharmacology, Case Western Reserve University, Cleveland, Ohio, USA; and Veterans Administration Medical Center Research Service 151, Cleveland, Ohio, USA.
Krzysztof Palczewski*Department of Medicine, Case Western Reserve University, Cleveland, Ohio, USA; Department of Ophthalmology and Visual Sciences, The University of Michigan, Ann Arbor, Michigan, USA; Department of Pharmacology, Case Western Reserve University, Cleveland, Ohio, USA; and Veterans Administration Medical Center Research Service 151, Cleveland, Ohio, USA.
Timothy S Kern*Department of Medicine, Case Western Reserve University, Cleveland, Ohio, USA; Department of Ophthalmology and Visual Sciences, The University of Michigan, Ann Arbor, Michigan, USA; Department of Pharmacology, Case Western Reserve University, Cleveland, Ohio, USA; and Veterans Administration Medical Center Research Service 151, Cleveland, Ohio, USA tsk@case.edu.
Case Western Reserve University · USUniversity of Michigan–Ann Arbor · USUnited States Department of Veterans Affairs · US

Funding

Regional Pilot And Feasibility Study Grants ProgramP30DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI WILLIAM H HERMAN · 2013 to 2026
$24.3M
TISSUE CULTURE AND HYBRIDOMA MODULEP30EY011373 · NEI · CASE WESTERN RESERVE UNIVERSITY · PI Irina A Pikuleva · 1997 to 2026
$17.7M
Pharmacological Treatment of Retinal DiseasesR24EY021126 · NEI · CASE WESTERN RESERVE UNIVERSITY · PI PALCZEWSKI, KRZYSZTOF · 2010 to 2014
$12.8M
MECHANISMS OF RETINAL VASCULAR PERMEABILITY IN DIABETESR01EY012021 · NEI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ANTONETTI, DAVID · 1998 to 2024
$8.6M
STUDY OF DIABETIC RETINOPATHYR01EY000300 · NEI · UNIVERSITY OF WISCONSIN MADISON · PI KERN, TIMOTHY S · 1985 to 2013
$4.7M
Role of Photoreceptors in the Pathogenesis of Diabetic RetinopathyR01EY022938 · NEI · UNIVERSITY OF CALIFORNIA-IRVINE · PI KERN, TIMOTHY S · 2013 to 2021
$3.7M
Vision Research CoreP30EY021721 · NEI · UNIVERSITY OF FLORIDA · PI HAUSWIRTH, WILLIAM W · 2011 to 2015
$2.8M
Acetylation and diabetic retinopathyI01BX002117 · VA · LOUIS STOKES CLEVELAND VA MEDICAL CENTER · PI KERN, TIMOTHY S · 2014 to 2017
–
BLRD VA I01 BX002117NEI NIH HHS P30 EY011373NEI NIH HHS P30 EY021721NEI NIH HHS P30EY11373NEI NIH HHS R01 EY000300NEI NIH HHS R01EY00300NEI NIH HHS R01 EY012021NEI NIH HHS R01 EY022938NEI NIH HHS R01EY022938NEI NIH HHS R24 EY021126NEI NIH HHS R24EY021126NIDDK NIH HHS P30 DK020572
6 · The paper itself

Abstract

Reactive oxygen species play an important role in the pathogenesis of diabetic retinopathy. We studied the role of adrenergic and serotonin receptors in the generation of superoxide by retina and 661W retinal cells in high glucose and of the α1-adrenergic receptor (AR) on vascular lesions of the retinopathy in experimentally diabetic C57Bl/6J mice (and controls) after 2 and 8 months. Compared with 5 mM glucose, incubating cells or retinal explants in 30 mM glucose induced superoxide generation. This response was reduced or ablated by pharmacologic inhibition of the α1-AR (a Gq-coupled receptor) or Gs-coupled serotonin (5-HT2, 5-HT4, 5-HT6, and 5-HT7) receptors or by activation of the Gi-coupled α2-AR. In elevated glucose, the α1-AR produced superoxide via phospholipase C, inositol triphosphate-induced Ca(2+) release, and NADPH oxidase, and pharmacologic inhibition of these reactions prevented the superoxide increase. Generation of retinal superoxide, expression of proinflammatory proteins, and degeneration of retinal capillaries in diabetes all were significantly inhibited with daily doxazosin or apocynin (inhibitors of α1-AR and NADPH oxidase, respectively), but increased vascular permeability was not significantly affected. Adrenergic receptors, and perhaps other GPCRs, represent novel targets for inhibiting the development of important features of diabetic retinopathy.

Indexed as

AnimalsCapillariesCells, CulturedCyclic AMPDiabetes Mellitus, ExperimentalDiabetic RetinopathyMaleMiceMice, Inbred C57BLReal-Time Polymerase Chain ReactionReceptors, AdrenergicReceptors, SerotoninRetinaRetinal DegenerationReverse Transcriptase Polymerase Chain ReactionRNA, MessengerCyclic AMPReceptors, AdrenergicReceptors, SerotoninRNA, MessengerSuperoxidesdiabetic retinopathyGPCRsinflammationNADPH oxidase

Identifiers

PMID25667222
PMCPMC4415023
OpenAlexW1995045917

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.