Evidence map›Paper›PMID 33963197›Full record

Trial reportScientific reports2021

Elevated dimethylarginine, ATP, cytokines, metabolic remodeling involving tryptophan metabolism and potential microglial inflammation characterize primary open angle glaucoma.

Sujith Kumar Pulukool, Sai Krishna Srimadh Bhagavatham, Vishnu Kannan, Piruthivi Sukumar, Rajesh Babu Dandamudi, Shamika Ghaisas, Haripriya Kunchala, Darshan Saieesh, Ashwin Ashok Naik, Ashish Pargaonkar and 2 more

Erratum issuedOpen access · goldAbstract readClinical Trial
In one paragraph

Trial report in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
4.7field-weighted citation impact, top 4% 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

19 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.

  1. Pooled it
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  13. Vitamin B3 Biotech · 2023
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  17. Damage-Associated Molecular Patterns (DAMPs) in Retinal Disorders.International journal of molecular sciences · 2022
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 6 institutions in 2 countries.

Sujith Kumar PulukoolDisease Biology Lab, SSSIHL-Agilent Center for Excellence in Multiomics and Cell Sciences, Dept. of Biosciences, Sri Sathya Sai Institute of Higher Learning, Prasanthi Nilayam, Anantapur, Andhra Pradesh, 515 134, India.
Sai Krishna Srimadh BhagavathamDisease Biology Lab, SSSIHL-Agilent Center for Excellence in Multiomics and Cell Sciences, Dept. of Biosciences, Sri Sathya Sai Institute of Higher Learning, Prasanthi Nilayam, Anantapur, Andhra Pradesh, 515 134, India.
Vishnu KannanDisease Biology Lab, SSSIHL-Agilent Center for Excellence in Multiomics and Cell Sciences, Dept. of Biosciences, Sri Sathya Sai Institute of Higher Learning, Prasanthi Nilayam, Anantapur, Andhra Pradesh, 515 134, India.
Piruthivi SukumarLeeds Institute of Cardiovascular and Metabolic Medicine, School of Medicine, University of Leeds, Leeds, UK.
Rajesh Babu DandamudiSSSIHL-Agilent Center for Excellence in Multiomics and Cell Sciences, Dept. of Chemistry, Sri Sathya Sai Institute of Higher Learning, Prasanthi Nilayam, Anantapur, Andhra Pradesh, 515 134, India.
Shamika GhaisasDepartment of Ophthalmology, Sri Sathya Sai Institute of Higher Medical Sciences, Prasanthi Gram, Anantapur, Andhra Pradesh, 515 134, India.
Haripriya KunchalaDepartment of Ophthalmology, Sri Sathya Sai Institute of Higher Medical Sciences, Prasanthi Gram, Anantapur, Andhra Pradesh, 515 134, India.
Darshan SaieeshDisease Biology Lab, SSSIHL-Agilent Center for Excellence in Multiomics and Cell Sciences, Dept. of Biosciences, Sri Sathya Sai Institute of Higher Learning, Prasanthi Nilayam, Anantapur, Andhra Pradesh, 515 134, India.
Ashwin Ashok NaikDisease Biology Lab, SSSIHL-Agilent Center for Excellence in Multiomics and Cell Sciences, Dept. of Biosciences, Sri Sathya Sai Institute of Higher Learning, Prasanthi Nilayam, Anantapur, Andhra Pradesh, 515 134, India.
Ashish PargaonkarApplication Division, Agilent Technologies Ltd., Bengaluru, India.
Anuj SharmaDepartment of Ophthalmology, Sri Sathya Sai Institute of Higher Medical Sciences, Prasanthi Gram, Anantapur, Andhra Pradesh, 515 134, India. anujsharma85@gmail.com.
Venketesh SivaramakrishnanDisease Biology Lab, SSSIHL-Agilent Center for Excellence in Multiomics and Cell Sciences, Dept. of Biosciences, Sri Sathya Sai Institute of Higher Learning, Prasanthi Nilayam, Anantapur, Andhra Pradesh, 515 134, India. s.venketesh@gmail.com.ORCID http://orcid.org/0000-0003-3094-5905
Sri Sathya Sai Institute of Higher Learning · INSri Sathya Sai Institute of Higher Medical Sciences · INAgilent Technologies (India) · INBioGenex (India) · INGovernment Medical College · INUniversity of Leeds · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Glaucoma of which primary open angle glaucoma (POAG) constitutes 75%, is the second leading cause of blindness. Elevated intra ocular pressure and Nitric oxide synthase (NOS) dysfunction are hallmarks of POAG. We analyzed clinical data, cytokine profile, ATP level, metabolomics and GEO datasets to identify features unique to POAG. N9 microglial cells are used to gain mechanistic insights. Our POAG cohort showed elevated ATP in aqueous humor and cytokines in plasma. Metabolomic analysis showed changes in 21 metabolites including Dimethylarginine (DMAG) and activation of tryptophan metabolism in POAG. Analysis of GEO data sets and previously published proteomic data sets bins genes into signaling and metabolic pathways. Pathways from reanalyzed metabolomic data from literature significantly overlapped with those from our POAG data. DMAG modulated purinergic signaling, ATP secretion and cytokine expression were inhibited by N-Ethylmaleimide, NO donors, BAPTA and purinergic receptor inhibitors. ATP induced elevated intracellular calcium level and cytokines expression were inhibited by BAPTA. Metabolomics of cell culture supernatant from ATP treated sets showed metabolic deregulation and activation of tryptophan metabolism. DMAG and ATP induced IDO1/2 and TDO2 were inhibited by N-Ethylmaleimide, sodium nitroprusside and BAPTA. Our data obtained from clinical samples and cell culture studies reveal a strong association of elevated DMAG, ATP, cytokines and activation of tryptophan metabolism with POAG. DMAG mediated ATP signaling, inflammation and metabolic remodeling in microglia might have implications in management of POAG.

Indexed as

Adenosine TriphosphateAqueous HumorArginineCytokinesFemaleGlaucoma, Open-AngleHumansInflammationMaleMicrogliaTryptophanAdenosine TriphosphateArginineCytokinesdimethylarginineTryptophan

Identifiers

PMID33963197
PMCPMC8105335
OpenAlexW3159464591

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.