Tear proteomics of orbital decompression for disfiguring exophthalmos in inactive thyroid‑associated ophthalmopathy

Jiang, Lijia; Rong, Ao; Wei, Rui-Li; Diao, Jiale; Wang, Wei

doi:10.3892/etm.2020.9383

Cited by 7 publications

(3 citation statements)

References 51 publications

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“…It is precisely the trend of this protein panel that allows to differentiate TAO from DED. Advances in tear proteomics enabled, later on, Jiang and coworkers to deepen TAO pathogenesis by looking for potential therapeutic targets (Jiang et al, 2020). Tears collected before and after orbital decompression in patients with inactive TAO were analyzed by LC‐MS/MS, with 83 proteins resulting differentially expressed among the two disease groups and healthy controls.…”

Section: Tears As An Unconventional Source Of Biomarkersmentioning

confidence: 99%

Mass spectrometry‐based tear proteomics for noninvasive biomarker discovery

Ponzini

Santambrogio

Palma

et al. 2021

Mass Spectrometry Reviews

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The lacrimal film has attracted increasing interest in the last decades as a potential source of biomarkers of physiopathological states, due to its accessibility, moderate complexity, and responsiveness to ocular and systemic diseases. High‐performance liquid chromatography‐mass spectrometry (LC‐MS) has led to effective approaches to tear proteomics, despite the intrinsic limitations in sample amounts. This review focuses on the recent progress in strategy and technology, with an emphasis on the potential for personalized medicine. After an introduction on lacrimal‐film composition, examples of applications to biomarker discovery are discussed, comparing approaches based on pooled‐sample and single‐tear analysis. Then, the most critical steps of the experimental pipeline, that is, tear collection, sample fractionation, and LC‐MS implementation, are discussed with reference to proteome‐coverage optimization. Advantages and challenges of the alternative procedures are highlighted. Despite the still limited number of studies, tear quantitative proteomics, including single‐tear investigation, could offer unique contributions to the identification of low‐invasiveness, sustained‐accessibility biomarkers, and to the development of personalized approaches to therapy and diagnosis.

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Section: Tears As An Unconventional Source Of Biomarkersmentioning

confidence: 99%

Mass spectrometry‐based tear proteomics for noninvasive biomarker discovery

Ponzini

Santambrogio

Palma

et al. 2021

Mass Spectrometry Reviews

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“…This evidence suggests that the two inflammation-related pathways might be involved in the occurrence and development of TAO, which may account for the lack of influence of tissue specificity. Similarly, growing evidence shows that some neuromodulation-related pathways may be involved in TAO [ 31 , 32 ]. Thus, inflammatory mechanisms and neuronal function may play important roles in the different lesion tissues of TAO.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of key genes and pathways for biological and clinical implications in thyroid-associated ophthalmopathy

et al. 2022

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Background Thyroid-associated ophthalmopathy (TAO) is a common and organ-specific autoimmune disease. Early diagnosis and novel treatments are essential to improve the prognosis of TAO patients. Therefore, the current work was performed to identify the key genes and pathways for the biological and clinical implications of TAO through comprehensive bioinformatics analysis and a series of clinical validations. Methods GSE105149 and GSE185952 were obtained from the Gene Expression Omnibus (GEO) database for analysis. The data were normalized to identify the common differentially expressed genes (DEGs) between the two datasets, and the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to assess key pathways in TAO. Protein–protein interaction (PPI) networks and hub genes among the common DEGs were identified. Furthermore, we collected the general information and blood samples from 50 TAO patients and 20 healthy controls (HCs), and the expression levels of the proteins encoded by hub genes in serum were detected by enzyme-linked immunosorbent assay (ELISA). Then we further assessed the relationship between the ELISA data and the TAO development. Results Several common pathways, including neuroactive ligand-receptor interaction, the IL-17 signaling pathway, and the TNF signaling pathway, were identified in both datasets. In parallel, 52 common DEGs were identified. The KEGG analysis showed that these common DEGs are mainly enriched in long-term depression, the VEGF signaling pathway, the IL-17 signaling pathway, the TNF signaling pathway, and cytokine-cytokine receptor interactions. The key hub genes PRKCG, OSM, DPP4, LRRTM1, CXCL6, and CSF3R were screened out through the PPI network. As confirmation, the ELISA results indicated that protein expression levels of PRKCG, OSM, CSF3R, and DPP4 were significantly upregulated in TAO patients compared with HCs. In addition, PRKCG and DPP4 were verified to show value in diagnosing TAO, and CSF3R was found to be a valuable diagnostic marker in distinguishing active TAO from inactive TAO. Conclusions Inflammation- and neuromodulation-related pathways might be closely associated with TAO. Based on the clinical verification, OSM, CSF3R, CXCL6, DPP4, and PRKCG may serve as inflammation- or neuromodulation-related biomarkers for TAO, providing novel insights for the diagnosis and treatment of TAO.

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“…The tears were collected in a sterile 1.5 mL centrifuge tube and stored in −80°C. 24 – 26 Tears were collected at the initial and the following two follow-up visits. The patients did not receive any anti-allergic treatment when their tears were collected for the first time.…”

Section: Methodsmentioning

confidence: 99%

Gp130 Promotes Inflammation via the STAT3/JAK2 Pathway in Allergic Conjunctivitis

Bao

Zhang

et al. 2023

Invest. Ophthalmol. Vis. Sci.

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Purpose Allergic conjunctivitis (AC) is a common allergic condition worldwide that requires accurate screening and early diagnosis. We found that gp130 is essential for AC, as gp130 levels are elevated in AC. Therefore, this study aimed to elucidate the functions and the possible underlying mechanisms of gp130 in AC. Methods To compare mRNA expression profiles, the conjunctival tissues of BALB/c mice with ovalbumin (OVA)-induced AC were subjected to RNA-sequencing (RNA-seq) analysis followed by bioinformatic analysis. A nonrandomized study involving 57 patients with AC and 24 sex- and age-matched healthy individuals was conducted. A protein chip was used to detect cytokine levels in patient tears. Differentially expressed proteins in patient serum were detected using label-free quantitative mass spectrometry. Histamine-stimulated conjunctival epithelial cells (HConEpiCs) were used to construct a cell model. LMT-28 which can inhibit gp130 phosphorylation was dropped onto the murine ocular surface, and the resulting symptoms were observed. Results Gp130 is upregulated in the conjunctival tissues of OVA-induced mice, the serum and tears of patients, and the histamine-stimulated HConEpiCs. Signal transducer and activator of transcription 3 (STAT3) and Janus kinase 2 (JAK2) were upregulated in the conjunctival tissues of mice with OVA-induced AC and in HConEpiCs. Ocular surface inflammation was significantly relieved in LMT-28-treated mice. The expression of IgE, IL-4, IL-5, and IL-13 in serum of LMT-28-treated mice decreased. The number of mast cells in conjunctival tissue was decreased compared with OVA-induced mice. Conclusions Gp130 may play an important role in AC via the gp130/JAK2/STAT3 pathway. Inhibiting gp130 phosphorylation alleviates ocular surface inflammation in mice, presenting a potential treatment approach for AC.

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Tear proteomics of orbital decompression for disfiguring exophthalmos in inactive thyroid‑associated ophthalmopathy

Cited by 7 publications

References 51 publications

Mass spectrometry‐based tear proteomics for noninvasive biomarker discovery

Mass spectrometry‐based tear proteomics for noninvasive biomarker discovery

Comprehensive analysis of key genes and pathways for biological and clinical implications in thyroid-associated ophthalmopathy

Gp130 Promotes Inflammation via the STAT3/JAK2 Pathway in Allergic Conjunctivitis

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