Thyroid-associated orbitopathy and tears: A proteomics study

Kishazi, Edina; Dor, Marianne; Eperon, Simone; Oberic, A.; Hamédani, M.; Turck, Natacha

doi:10.1016/j.jprot.2017.09.001

Cited by 32 publications

(29 citation statements)

References 27 publications

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“…Globally, our findings obtained for TNF-α, IL-6, IL-8 IL-10 and IL-13 were completely relevant of TAO and confirmed previous studies on tears 5 , 18 , 19 but also on serum 19 – 22 , 25 . They also confirmed some results that we obtained performing quantitative proteomics analyses with mass spectrometry 26 . Our major result was that two proteins related to the inflammation, cystatin C and serpin A3, were found significantly upregulated in tears of TAO patients compared to controls (ratio TAO/controls = 1.53 for cystatin and 1.7 for serpinA3).…”

Section: Discussionsupporting

confidence: 89%

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Differential profiling of lacrimal cytokines in patients suffering from thyroid-associated orbitopathy

Kishazi

Dor

Eperon

et al. 2018

Sci Rep

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The aim was to investigate the levels of cytokines and soluble IL-6R in the tears of patients with thyroid-associated orbitopathy (TAO) disease. Schirmer’s test was adopted to collect tears from TAO patients (N = 20, 17 women, mean age (±SD): 46.0 years (±13.4)) and healthy subjects (N = 18, 10 women, 45.4 years (±18.7)). Lacrimal cytokines and soluble IL-6R (sIL-6R) were measured using a 10-plex panel (Meso Scale Discovery Company) and Invitrogen Human sIL-6R Elisa kit, respectively. Tear levels of IL-10, IL-12p70, IL-13, IL-6 and TNF-α appeared significantly higher in TAO patients than in healthy subjects. Interestingly, IL-10, IL-12p70 and IL-8 levels increased in tears whatever the form of TAO whereas IL-13, IL-6 and TNF-α levels were significantly elevated in inflammatory TAO patients, meaning with a clinical score activity (CAS) ≥ 3, compared to controls. Furthermore, only 3 cytokines were strongly positively correlated with CAS (IL-13 Spearman coeff. r: 0.703, p = 0.0005; IL-6 r: 0.553, p = 0.011; IL-8 r: 0.618, p = 0.004, respectively). Finally, tobacco use disturbed the levels of several cytokines, especially in patient suffering of TAO. The differential profile of lacrimal cytokines could be useful for the diagnosis of TAO patients. Nevertheless, the tobacco use of these patients should be taken into account in the interpretation of the cytokine levels.

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Section: Discussionsupporting

confidence: 89%

“…Patients wearing lenses and pregnant women were also excluded. Among the collected samples, 10 out of the 18 controls and 6 out of the 20 TAO patients were also used in the proteomics study that we carried in parallel 26 .…”

Section: Methodsmentioning

confidence: 99%

Differential profiling of lacrimal cytokines in patients suffering from thyroid-associated orbitopathy

Kishazi

Dor

Eperon

et al. 2018

Sci Rep

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“…External factors such as harsh lighting, background noise and extreme room temperature, all known to affect the content of samples, were strictly supervised in order to ensure satisfactory reproducibility. The strip was then inserted in a tube on ice and centrifuged at g for 7 min at 4°C without any additional buffer, as described elsewhere (17)(18)(19). After centrifugation, tear samples were immediately stored at -80°C until analysis.…”

Section: Sample Collectionmentioning

confidence: 99%

Investigation of the global protein content from healthy human tears

Dor

Eperon

Lalive

et al. 2019

Experimental Eye Research

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Considering absence of invasiveness and side effects, tears emerge as a particularly attractive fluid for biomarker discovery and therefore for daily clinical use. However, to date, this fluid remains poorly studied in healthy condition. Here, we present an updated in-depth characterisation of the human healthy tear protein composition using proteomics approach. Both eyes of eight healthy controls were collected using the Schirmer's strip method. After liquid digestion and off-gel electrophoresis fractionation, three independent proteomics analyses were performed. Resulting files were searched against the uniprot_swissprot database (2017_05_10) using Thermo Proteome Discoverer (version 2.2) and a false discovery rate of 1% was selected. Globally, 1351 proteins were identified with 2 unique peptides. More specifically, 39% of the lacrimal proteins were enzymes, with high numbers of dehydrogenases, phosphatases, kinases and ligases. Immunoglobulins, serpins and 14-3-3 domains proteins emerged also as abundant lacrimal proteins. Pathway analyses highlighted among others the glycolysis and the coagulation and complement cascades. Our study therefore complements the existing data on healthy tears proteome. Nevertheless, extensive studies for deeply and definitively characterise this promising fluid are required in the near future in order to be able to routinely use this fluid in clinics. A better understanding of its protein content will probably open new avenues in the biomarker discovery and clinical practice in the near future.

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“…However, when the conjunctiva is stimulated abnormally, the protein overflow from the ocular surface vessels changes significantly (15). Previous studies have confirmed that numerous proteins are changed significantly in the tears of patients with TAO compared with in tears from healthy individuals (16,17). For example, α-1-antichymotrypsin, cystatin-C, interleukin (IL)-1β and IL-6 were upregulated, whereas phospholipase A 2 , STAT1-α/β, abhydrolase domain containing 14B and S100A4 were downregulated in patients with TAO (9,(18)(19)(20)(21).…”

Section: Tear Proteomics Of Orbital Decompression For Disfiguring Exomentioning

confidence: 95%

“…For example, IL-7 was reduced in tears from patients with active TAO, whereas its levels were increased in tears from patients with inactive TAO, when both were compared with those found in tears from healthy individuals (22). Previous studies (16)(17)(18)(19)(20)(21)(22) on the tear proteomics of TAO have mostly focused on active or mixed-status patients, and tear proteomics in TAO cases in the inactive stage have yet to be properly investigated. In addition, changes in tear proteomics before and after orbital decompression surgery have yet to be studied.…”

Section: Tear Proteomics Of Orbital Decompression For Disfiguring Exomentioning

confidence: 99%

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

et al. 2020

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The progress and achievements that have been made in tear proteomics in thyroid-associated ophthalmopathy (TAO) are critical for exploring the pathogenesis of TAO and investigating potential therapeutic targets. However, the tear proteomics of orbital decompression for disfiguring exophthalmos in inactive TAO have yet to be properly investigated. In the present study, orbital decompression was performed to repair disfiguring exophthalmos in patients with inactive TAO. Tears were collected before and after orbital decompression in patients with inactive TAO. Liquid chromatography with tandem mass spectrometry (LC-MS/MS) was performed to explore the changes in tear proteomics. Bioinformatics analyses were then employed to analyze the functions of the differentially expressed proteins (DEPs) identified by LC-MS/MS. The palpebral fissure height and exophthalmia area were significantly restored after 1 month of orbital decompression such that they approached the normal levels identified in healthy eyeballs. Among the 669 proteins identified by LC-MS/MS, 83 proteins were changed significantly between the preoperative and postoperative stages in inactive TAO patients and healthy control individuals. The DEPs were predicted to be involved in numerous signaling pathways. Bioinformatics analyses revealed that pathways associated with the immune system, metabolism, programmed cell death, vesicle-mediated transport, neuronal system and extracellular matrix organization may fulfill significant roles in orbital decompression in patients with inactive TAO. Taken together, these results provided a preliminary understanding of the mechanism of orbital decompression for disfiguring exophthalmos in inactive TAO patients.

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Thyroid-associated orbitopathy and tears: A proteomics study

Cited by 32 publications

References 27 publications

Differential profiling of lacrimal cytokines in patients suffering from thyroid-associated orbitopathy

Differential profiling of lacrimal cytokines in patients suffering from thyroid-associated orbitopathy

Investigation of the global protein content from healthy human tears

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

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