Dataset Information

Multi-Omics Approach for Studying Tears in Treatment-Naive Glaucoma Patients.

ABSTRACT: Primary open-angle glaucoma (POAG) represents the leading cause of irreversible blindness worldwide and is a multifactorial, chronic neurodegenerative disease characterized by retinal ganglion cell and visual field loss. There are many factors that are associated with the risk of developing POAG, with increased intraocular pressure being one of the most prevalent. Due to the asymptomatic nature of the disease, the diagnosis of POAG often occurs too late, which necessitates development of new effective screening strategies for early diagnosis of the disease. However, this task still remains unfulfilled. In order to provide further insights into the pathophysiology of POAG, we applied a targeted metabolomics strategy based on a high-throughput screening method for the determination of tear amino acids, free carnitine, acylcarnitines, succinylacetone, nucleosides, and lysophospholipids in naïve to therapy glaucomatous patients and normal controls. Also, we conducted proteomic analyses of the whole lacrimal fluid and purified extracellular vesicles obtained from POAG patients and healthy subjects. This multi-omics approach allowed us to conclude that POAG patients had lower levels of certain tear amino acids and lysophospholipids compared with controls. These targeted analyses also highlighted the low amount of acetylcarnitine (C2) in POAG patient which correlated well with proteomics data. Moreover, POAG tear proteins seemed to derive from extracellular vesicles, which carried a specific pro-inflammatory protein cargo.

SUBMITTER: Rossi C

PROVIDER: S-EPMC6721157 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Multi-Omics Approach for Studying Tears in Treatment-Naïve Glaucoma Patients.

Rossi Claudia C Cicalini Ilaria I Cufaro Maria Concetta MC Agnifili Luca L Mastropasqua Leonardo L Lanuti Paola P Marchisio Marco M De Laurenzi Vincenzo V Del Boccio Piero P Pieragostino Damiana D

International journal of molecular sciences 20190818 16

Primary open-angle glaucoma (POAG) represents the leading cause of irreversible blindness worldwide and is a multifactorial, chronic neurodegenerative disease characterized by retinal ganglion cell and visual field loss. There are many factors that are associated with the risk of developing POAG, with increased intraocular pressure being one of the most prevalent. Due to the asymptomatic nature of the disease, the diagnosis of POAG often occurs too late, which necessitates development of new eff ...[more]

PMID: 31426571

Similar Datasets

Project description:PurposeTo explore patients' perspectives and experiences living with moderate to severe glaucoma through qualitative, semistructured interviews and to identify important benefits and risks that patients consider when choosing glaucoma treatments.DesignSemistructured, in-person qualitative interviews with a convenience sample of patients seen at the Johns Hopkins Wilmer Eye Institute.ParticipantsSurgery-naive patients 21 years of age or older with moderate to severe open-angle glaucoma seeking treatment at the Wilmer Eye Institute's Glaucoma Center of Excellence between August and December 2018.MethodsWe conducted semistructured interviews with patients diagnosed with moderate to severe open-angle glaucoma, focusing on outcomes they prioritize when considering various treatment options. We used Atlas.ti software version 7.5.12 (Scientific Software Development GmbH, Berlin, Germany) to process interview transcripts and the framework approach to analyze the qualitative data.Main outcome measuresPatients' descriptions of outcomes important to them in management of moderate to severe open-angle glaucoma.ResultsThirteen men and 15 women with a median age 67 years participated in the study. Compared with the mild-to-moderate glaucoma patients interviewed previously, these participants similarly emphasized (1) activities of daily living, (2) visual symptoms, (3) treatment burden, and (4) intraocular pressure (IOP) control, but unlike patients with milder disease, most related IOP control directly to (5) avoiding disease progression. Almost all (27/28) had also given significant thought to (6) surgical decision making and could describe how they would decide for or against a particular procedure. Finally, two thirds (18/28) expressed (7) significant fear and worry related to their glaucoma diagnosis.ConclusionsWe identified outcomes that matter to patients who are undergoing treatment for moderate to severe glaucoma, many of which may serve as end points in clinical trials, such as functional independence in vision-dependent activities of daily living, avoidance of visual symptoms, and disease progression via maintenance of IOP control. We also observed that these patients have varied and nuanced perspectives on surgical management and its outcomes. It behooves providers and trial designers to consider these in future evaluations of new treatments for moderate to severe glaucoma.

Project description:The most aggressive primary malignant brain tumor in adults is glioblastoma (GBM), which has poor overall survival (OS). There is a high relapse rate among patients with GBM despite maximally safe surgery, radiation therapy, temozolomide (TMZ), and aggressive treatment. Hence, there is an urgent and unmet clinical need for new approaches to managing GBM. The current study identified modules (MYC, EGFR, PIK3CA, SUZ12, and SPRK2) involved in GBM disease through the NeDRex plugin. Furthermore, hub genes were identified in a comprehensive interaction network containing 7560 proteins related to GBM disease and 3860 proteins associated with signaling pathways involved in GBM. By integrating the results of the analyses mentioned above and again performing centrality analysis, eleven key genes involved in GBM disease were identified. ProteomicsDB and Gliovis databases were used for determining the gene expression in normal and tumor brain tissue. The NetworkAnalyst and the mGWAS-Explorer tools identified miRNAs, SNPs, and metabolites associated with these 11 genes. Moreover, a literature review of recent studies revealed other lists of metabolites related to GBM disease. The enrichment analysis of identified genes, miRNAs, and metabolites associated with GBM disease was performed using ExpressAnalyst, miEAA, and MetaboAnalyst tools. Further investigation of metabolite roles in GBM was performed using pathway, joint pathway, and network analyses. The results of this study allowed us to identify 11 genes (UBC, HDAC1, CTNNB1, TRIM28, CSNK2A1, RBBP4, TP53, APP, DAB1, PINK1, and RELN), five miRNAs (hsa-mir-221-3p, hsa-mir-30a-5p, hsa-mir-15a-5p, hsa-mir-130a-3p, and hsa-let-7b-5p), six metabolites (HDL, N6-acetyl-L-lysine, cholesterol, formate, N, N-dimethylglycine/xylose, and X2. piperidinone) and 15 distinct signaling pathways that play an indispensable role in GBM disease development. The identified top genes, miRNAs, and metabolite signatures can be targeted to establish early diagnostic methods and plan personalized GBM treatment strategies.

Dataset Information

Multi-Omics Approach for Studying Tears in Treatment-Naive Glaucoma Patients.

Publications

Multi-Omics Approach for Studying Tears in Treatment-Naïve Glaucoma Patients.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets