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ORIGINAL RESEARCH article

Front. Mol. Biosci.
Sec. Metabolomics
Volume 11 - 2024 | doi: 10.3389/fmolb.2024.1421030
This article is part of the Research Topic Metabolomics in Human and Animal Ophthalmic Research View all articles

Integrated clinical and metabolomic analysis identifies molecular signatures, Biomarkers and Therapeutic Targets in Primary angle closure glaucoma

Provisionally accepted
Vishnu Kannan Vishnu Kannan 1Sai Krishna Srimadh Bhagavatham Sai Krishna Srimadh Bhagavatham 1Rajesh Babu Dandamudi Rajesh Babu Dandamudi 1Haripriya Kunchala Haripriya Kunchala 2Siva Teja Challa Siva Teja Challa 2Abdulrahman I. Almansour Abdulrahman I. Almansour 3Ashish Pargaonkar Ashish Pargaonkar 4Sujith Kumar Sujith Kumar 1Anuj Sharma Anuj Sharma 2Venketesh Sivaramakrishnan Venketesh Sivaramakrishnan 5*
  • 1 Sri Sathya Sai Institute of Higher Learning (SSSIHL), Anantapur, Andhra Pradesh, India
  • 2 Sri Sathya Sai Institute of Higher Medical Sciences, Puttaparthi, Andhra Pradesh, India
  • 3 College of Science, King Saud University, Riyadh, Saudi Arabia
  • 4 Agilent Technologies (India), Gurgaon, Haryana, India
  • 5 Department of Biosciences, Sri Sathya Sai Institute of Higher Learning (SSSIHL), Anantapur, Andhra Pradesh, India

The final, formatted version of the article will be published soon.

    Background: Glaucoma is the leading cause of permanent blindness. Primary angle closure glaucoma (PACG) is diagnosed only after the onset of symptoms resulting in irreversible blindness despite the standard intraocular pressure (IOP) reduction therapy. The identification of potential biomarkers associated with prognosis will help improve disease management. This study aimed to identify mechanisms associated with disease progression, potential biomarkers and therapeutic targets of PACG. Methods: The Clinical data assessment of IOP, cup/disc ratio (CDR) and Retinal Nerve fiber layer (RNFL) thickness of control and PACG group were collected and analyzed for significant differences. The ATP estimation and targeted metabolomic analysis on aqueous humor and cytokine in plasma were performed. The pathways obtained from metabolomics data set was compared with those obtained for data sets from literature. Correlation of clinical parameters were performed with cytokines. Targeted metabolomic analysis of cell culture supernatant from TNFα treated N9 microglia was carried out and overlap analysis was performed with data obtained from PACG patients. Results: Elevated IOP, CDR, ATP, cytokines and reduced RNFL thickness was found in PACG compared to controls. Analysis of PACG and TNFα treated N9 microglial cell culture supernatant shows activation of immunometabolites. The metabolic pathways of PACG, TNFα and ATP treated microglia from the literature show considerable overlap. Biomarker analysis conjured clinical parameters, ATP, cytokines and immunometabolites. Conclusions: This study shows an association of elevated levels of ATP, cytokines, immuno-metabolism and potential microglial inflammation with disease progression rendering them potential biomarkers. P2 receptors, cytokines and IDO1/2 could be potential therapeutic targets.

    Keywords: Glaucoma, Metabolomics, Inflammation, PACG, Immunometabolism

    Received: 21 Apr 2024; Accepted: 17 Jul 2024.

    Copyright: © 2024 Kannan, Srimadh Bhagavatham, Dandamudi, Kunchala, Challa, Almansour, Pargaonkar, Kumar, Sharma and Sivaramakrishnan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Venketesh Sivaramakrishnan, Department of Biosciences, Sri Sathya Sai Institute of Higher Learning (SSSIHL), Anantapur, 515 134, Andhra Pradesh, India

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