Vishnu Kannan, Sai Krishna Srimadh Bhagavatham, R. Dandamudi, Haripriya Kunchala, Sivateja Challa, A. Almansour, Ashish Pargaonkar, S. Pulukool, Anuj Sharma, Venketesh Sivaramakrishnan
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引用次数: 0
Abstract
Glaucoma is the leading cause of permanent blindness. Primary angle closure glaucoma (PACG) is diagnosed only after the onset of symptoms and can result 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.The clinical data assessment of IOP, cup/disc ratio (CDR), Retinal Nerve Fiber Layer (RNFL) thickness of control, and PACG group were collected and analyzed for significant differences. The ATP levels were estimated, and targeted metabolomic analysis was performed on aqueous humor and cytokines in plasma. The pathways obtained from the metabolomics data set were compared with those obtained for data sets from the literature. Clinical parameters were correlated with cytokine levels. 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.Elevated IOP, CDR, ATP, cytokines, and reduced RNFL thickness were found in PACG compared to controls. Analysis of PACG and TNFα-treated N9 microglial cell culture supernatant shows activation of immuno-metabolites. The metabolic pathways of PACG, TNFα, and ATP-treated microglia from the literature show considerable overlap. Biomarker analysis identified clinical parameters, ATP, cytokines, and immuno-metabolites.This study shows an association between elevated levels of ATP, cytokines, immuno-metabolism, and potential microglial inflammation with disease progression, rendering these levels potential biomarkers. P2 receptors, cytokines, and IDO1/2 could be potential therapeutic targets.
期刊介绍:
Much of contemporary investigation in the life sciences is devoted to the molecular-scale understanding of the relationships between genes and the environment — in particular, dynamic alterations in the levels, modifications, and interactions of cellular effectors, including proteins. Frontiers in Molecular Biosciences offers an international publication platform for basic as well as applied research; we encourage contributions spanning both established and emerging areas of biology. To this end, the journal draws from empirical disciplines such as structural biology, enzymology, biochemistry, and biophysics, capitalizing as well on the technological advancements that have enabled metabolomics and proteomics measurements in massively parallel throughput, and the development of robust and innovative computational biology strategies. We also recognize influences from medicine and technology, welcoming studies in molecular genetics, molecular diagnostics and therapeutics, and nanotechnology.
Our ultimate objective is the comprehensive illustration of the molecular mechanisms regulating proteins, nucleic acids, carbohydrates, lipids, and small metabolites in organisms across all branches of life.
In addition to interesting new findings, techniques, and applications, Frontiers in Molecular Biosciences will consider new testable hypotheses to inspire different perspectives and stimulate scientific dialogue. The integration of in silico, in vitro, and in vivo approaches will benefit endeavors across all domains of the life sciences.