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Transcriptome Analysis of Orbital Adipose Tissue in Active Thyroid Eye Disease Using Next Generation RNA Sequencing Technology.

ABSTRACT: Objective:This study utilized Next Generation Sequencing (NGS) to identify differentially expressed transcripts in orbital adipose tissue from patients with active Thyroid Eye Disease (TED) versus healthy controls. Method:This prospective, case-control study enrolled three patients with severe, active thyroid eye disease undergoing orbital decompression, and three healthy controls undergoing routine eyelid surgery with removal of orbital fat. RNA Sequencing (RNA-Seq) was performed on freshly obtained orbital adipose tissue from study patients to analyze the transcriptome. Bioinformatics analysis was performed to determine pathways and processes enriched for the differential expression profile. Quantitative Reverse Transcriptase-Polymerase Chain Reaction (qRT-PCR) was performed to validate the differential expression of selected genes identified by RNA-Seq. Results:RNA-Seq identified 328 differentially expressed genes associated with active thyroid eye disease, many of which were responsible for mediating inflammation, cytokine signaling, adipogenesis, IGF-1 signaling, and glycosaminoglycan binding. The IL-5 and chemokine signaling pathways were highly enriched, and very-low-density-lipoprotein receptor activity and statin medications were implicated as having a potential role in TED. Conclusion:This study is the first to use RNA-Seq technology to elucidate differential gene expression associated with active, severe TED. This study suggests a transcriptional basis for the role of statins in modulating differentially expressed genes that mediate the pathogenesis of thyroid eye disease. Furthermore, the identification of genes with altered levels of expression in active, severe TED may inform the molecular pathways central to this clinical phenotype and guide the development of novel therapeutic agents.

SUBMITTER: Lee BW

PROVIDER: S-EPMC5906971 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Transcriptome Analysis of Orbital Adipose Tissue in Active Thyroid Eye Disease Using Next Generation RNA Sequencing Technology.

Lee Bradford W BW Kumar Virender B VB Biswas Pooja P Ko Audrey C AC Alameddine Ramzi M RM Granet David B DB Ayyagari Radha R Kikkawa Don O DO Korn Bobby S BS

The open ophthalmology journal 20180416

<h4>Objective</h4>This study utilized Next Generation Sequencing (NGS) to identify differentially expressed transcripts in orbital adipose tissue from patients with active Thyroid Eye Disease (TED) <i>versus</i> healthy controls.<h4>Method</h4>This prospective, case-control study enrolled three patients with severe, active thyroid eye disease undergoing orbital decompression, and three healthy controls undergoing routine eyelid surgery with removal of orbital fat. RNA Sequencing (RNA-Seq) was pe ...[more]

PMID: 29760827

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Project description:BackgroundThyroid eye disease (TED) is the most frequent orbital disease in adults and is characterized by the accumulation of orbital adipose tissue (OAT). It can lead to eyelid retraction or even vision loss. Orbital decompression surgery serves as the primary treatment for inactive TED by removing the excess OAT. However, there is a lack of alternative treatments to surgery due to the unclear understanding of the pathogenesis, particularly the metabolic features. Accordingly, our study was implemented to explore the content and features of metabolites of OATs from TED patients.MethodThe OATs used in the current study were obtained from the orbital decompression surgery of seven patients with inactive TED. We also collected control OATs from eye surgical samples of five individuals with no history of autoimmune thyroid diseases, TED, or under non-inflammatory conditions. The liquid chromatography mass spectrometer was used for the measurements of the targeted metabolites. Afterwards, we performed differential metabolite assay analysis and related pathway enrichment analysis.ResultsIn our study, a total of 149 metabolite profiles were detected in all participants. There were significant differences in several metabolite profiles between the TED group and the control group, mainly including uric acid, oxidized glutathione, taurine, dGMP, oxidized glutathione 2, uracil, hexose-phosphate, 1-methylnicotinamide, D-sedoheptulose 1,7-bisphosphate, and uridine 5'-monophosphate (all p-value < 0.05). The TED-related pathways identified included purine metabolism, beta-alanine metabolism, glutathione metabolism (p-values < 0.05). Our study found overlaps and differences including uric acid and uracil, which are in accordance with metabolites found in blood of patients with TED from previous study and several newly discovered metabolite by our study such as hexose-phosphate, 1-methylnicotinamide, D-sedoheptulose 1,7-bisphosphate, compared to those tested from blood, OAT, or urine samples reported in previous studies.ConclusionThe findings of our study shed light on the metabolic features of OAT in individuals with TED. These results may help identify new treatment targets for TED, providing potential avenues for developing alternative treatments beyond ophthalmic surgery.

Dataset Information

Transcriptome Analysis of Orbital Adipose Tissue in Active Thyroid Eye Disease Using Next Generation RNA Sequencing Technology.

Publications

Transcriptome Analysis of Orbital Adipose Tissue in Active Thyroid Eye Disease Using Next Generation RNA Sequencing Technology.

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