Evidence map›Paper›PMID 30054947›Full record

ArticleJournal of cellular biochemistry2018

Critical role of endoplasmic reticulum stress in chronic endothelial activation-induced visual deficits in tie2-tumor necrosis factor mice.

Raji Lenin, Peter G Nagy, Shanta Alli, Vidhya R Rao, Matthias A Clauss, Uday B Kompella, Rajashekhar Gangaraju

Abstract read
In one paragraph

Article in Journal of cellular biochemistry, 2018. 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
3.2field-weighted citation impact, top 8% 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, 25 citations in OpenAlex.

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  6. Tauroursodeoxycholic Acid Alleviates Endoplasmic Reticulum Stress-Mediated Visual Deficits in Diabetic tie2-TNF Transgenic Mice via TGR5 Signaling.Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2023
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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

7 authors at 4 institutions in 1 country.

Raji LeninDepartment of Ophthalmology, University of Tennessee Health Science Center, Memphis, Tennessee.
Peter G NagyDepartment of Ophthalmology, University of Tennessee Health Science Center, Memphis, Tennessee.
Shanta AlliDepartment of Ophthalmology, University of Tennessee Health Science Center, Memphis, Tennessee.
Vidhya R RaoDepartment of Molecular Pharmacology and Experimental Therapeutics, Loyola University, Chicago, Illinois.
Matthias A ClaussDepartment of Cellular & Integrative Physiology, Indiana University, Indianapolis, Indiana.
Uday B KompellaSkaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, Colorado.
Rajashekhar GangarajuDepartment of Ophthalmology, University of Tennessee Health Science Center, Memphis, Tennessee.ORCID 0000-0002-6664-8286
University of Tennessee Health Science Center · USIndiana University Indianapolis · USLoyola University Chicago · USUniversity of Colorado Anschutz Medical Campus · US

Funding

Vascular and Neuronal Repair with Adipose Stromal Cells in RetinopathyR01EY023427 · NEI · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · PI GANGARAJU, RAJASHEKHAR · 2013 to 2017
$1.8M
NEI NIH HHS R01 EY023427
6 · The paper itself

Abstract

Diabetic retinopathy (DR) is the leading cause of vision loss among working-age adults. The interplay between hyperglycemia and endothelial activation in inducing endoplasmic reticulum (ER) stress pathways and visual deficits in DR is not fully understood. To address this, we used a mouse model of chronic vascular activation using endothelial-specific tumor necrosis factor-α (TNF-α)-expressing (tie2-TNF) mice to induce diabetes with streptozotocin. At 4 weeks post streptozotocin, a significant 2-fold to 10-fold increase in retinal neurovascular inflammatory gene transcript response in tie2-TNF mice was further increased in diabetic tie2-TNF mice. A decrease in visual acuity and scotopic b-wave amplitude in tie2-TNF mice was further accentuated in diabetic tie2-TNF mice and these changes correlated with a multi-fold increase in retinal ER stress markers and a reduction in adherens junctions. Cultured retinal endothelial cells showed a significant decrease in trans-endothelial resistance as well as VE-cadherin expression under TNF-α and high glucose stress. These changes were partly rescued by tauroursodeoxycholic acid, a potent ER stress inhibitor. Taken together, constant endothelial activation induced by TNF-α further exacerbated by hyperglycemia results in activation of ER stress and chronic proinflammation in a feed forward loop ultimately resulting in endothelial junction protein alterations leading to visual deficits in the retina. Inhibition of ER stress and endothelial activation may prove to be a novel therapeutic target in DR.

Indexed as

Analysis of VarianceAnimalsCell LineDiabetes Mellitus, ExperimentalDiabetic RetinopathyDisease Models, AnimalElectroretinographyEndoplasmic ReticulumEndoplasmic Reticulum StressEndothelial CellsGene ExpressionHumansInflammationMiceMice, Inbred C57BLMice, TransgenicReceptor, TIE-2StreptozocinTEK protein, humanTumor Necrosis Factor-alphaendoplasmic reticulum stressERGhyperglycemiainflammationoptokinetic measurements and diabetic retinopathytauroursodeoxycholic acidtumor necrosis factorunfolded protein response

Identifiers

PMID30054947
PMCPMC6186177
OpenAlexW2883570204

What Socratic holds

Textmetadata
LicenceTDM
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 Socratic graph.