A Tear Metabolomic Profile Showing Increased Ornithine Decarboxylase Activity and Spermine Synthesis in Thyroid-Associated Orbitopathy

Billiet, Benjamin; Barca, Juan Manuel Chao de la; Ferré, Marc; Muller, Jeanne; Vautier, Anaïs; Assad, S.; Blanchet, Odile; Tessier, Lydie; Wetterwald, Céline; Faure, Justine; Urbanski, G.; Simard, Gilles; Mirebeau‐Prunier, Delphine; Rodien, Patrice; Gohier, Philippe; Reynier, Pascal

doi:10.3390/jcm11020404

Cited by 8 publications

(5 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, there is no overlap between the reported metabolites in Dong Yoon Ji's study compared with the detected metabolites in our study. On the other hand, we found that the level of spermine was downregulated in the OAT of patients with TED rather than upregulated in tears of patients with TED reported by Benjamin Billiet's study (10). However, in Dong Yoon Ji's study, they did not distinguish inactive or active stage of TED in their participants.…”

Section: Discussioncontrasting

confidence: 69%

“…Moreover, Ujheli et al showed that the concentrations of plasminogen activator inhibitor-1, IL-17A, IL-18, IL-13, and IL-6 were increased in tear samples collected from patients with TED compared with controls without TED (9). Benjamin Billiet et al reported elevated level of spermine in the tears of patients with active TED (10). Apart from biomarkers in tears, metabolites and lipidomic profiles in the blood and the orbital tissue of patients with TED also warrants further investigation.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, several studies have reported that metabolic biomarkers in tears of TED patients exhibited important implication for the metabolic distinguishment of TED (8)(9)(10). Similarly, potential candidate metabolic markers for differentiating the state of TED based on plasma or urinary lipidomic analysis were also reported (11).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Metabolic features of orbital adipose tissue in patients with thyroid eye disease

Wang

Yang

et al. 2023

Front. Endocrinol.

View full text Add to dashboard Cite

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.

show abstract

Section: Discussioncontrasting

confidence: 69%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Metabolic features of orbital adipose tissue in patients with thyroid eye disease

Wang

Yang

et al. 2023

Front. Endocrinol.

View full text Add to dashboard Cite

show abstract

“…Thus, knowledge of a patient’s tear metabolome can extend the diagnostic potential of TAO. Following a study performed by Billiet et al [ 50 ] using mass spectrometry, wherein the accurate measurement of 44 metabolites to compare the metabolic composition of tears in patients with active versus inactive TAO was performed. Two short-chain acylcarnitines, propionylcarnitine and butyrylcarnitine, and spermine were reported with increased concentrations in the tears of patients with active TAO.…”

Section: Markers In the Tears Of Patients With Graves’ Orbitopathymentioning

confidence: 99%

Tears as a Source of Biomarkers in the Diagnosis of Graves’ Orbitopathy

et al. 2022

View full text Add to dashboard Cite

Thyroid eye disease (TED) is a poorly understood autoimmune manifestation of thyroid diseases most commonly associated with Graves’ disease. Due to a lack of specific biomarkers and uncertain signs and symptoms, Graves’ orbitopathy (GO) is challenging to diagnose early and treat effectively. Nowadays, there is great interest in searching for precise molecular biomarkers for early detection, disease monitoring, and clinical management. Researchers are keen to identify novel methods to predict and diagnose diseases and to monitor patient therapeutic response. Tears, due to their direct contact with the eye and the fact that lacrimal glands can also be affected by the disease, could give new insights into the mechanisms taking place in thyroid-associated orbitopathy (TAO) and reveal potential promising biomarkers. Tear fluid offers the possibility of the non-invasive acquisition of a sample with a high protein content, thereby attracting continuously growing interest in the discovery of novel biomarkers. This article provides an up-to-date overview of the various putative tear-fluid biomarkers that have been identified. In this review, we present the potential use of tears as a diagnostic fluid and tool to investigate the mechanism of ocular diseases and discuss the future research directions in this area.

show abstract

“…In GO patients, the evaporation of tears may be caused by long-term ocular exposure because of eyelid retraction and proptosis ( 5 ). Studies have shown that lacrimal glands in GO patients are involved in autoimmune responses, leading to changes in the composition of tears ( 6 ). Therefore, changes in tears and lacrimal glands might be considered risk factors for progression in GO patients ( 7 ).…”

Section: Introductionmentioning

confidence: 99%

Tear-derived exosomal biomarkers of Graves’ ophthalmopathy

et al. 2022

View full text Add to dashboard Cite

Graves’ ophthalmopathy (GO), the most frequent extrathyroidal manifestation of Graves’ disease (GD), can lead to a significant decline in the quality of life in patients. Exosomes, which contain proteins, lipids and DNA, play important roles in the pathological processes of various diseases. However, their roles in Graves’ ophthalmopathy are still unclear. We aimed to isolate exosomes and analyze the different exosomal proteins. Tear fluids were collected from twenty-four GO patients, twenty-four GD patients and sixteen control subjects. The numbers of tear exosomes were assayed using nanoparticle tracking analysis. A Luminex 200 kit and ELISA kit were used to confirm the different cytokine concentrations in serum. Extraocular muscle from GO patients and controls was extracted, and western blotting was used to assay the levels of Caspase-3 and complement C4A. Our study demonstrated that the number of tear exosomes differ from GD patients and control. The expression levels of cytokines, including IL-1 and IL-18, were significantly increased in the tear exosomes and serum from GO patients compared with GD patients and controls. The levels of the exosomal proteins Caspase-3, complement C4A and APOA-IV were significantly increased in GO patients compared to GD patients and controls. Orbital fibroblasts from GO patients showed significantly higher levels of Caspase-3 and complement C4A than those from controls. The levels of serum APOA-IV in GO patients were significantly higher than those in GD patients and controls. Specific proteins showed elevated expression in tear exosomes from GO patients, indicating that they may play important roles in GO pathogenesis.

show abstract

A Tear Metabolomic Profile Showing Increased Ornithine Decarboxylase Activity and Spermine Synthesis in Thyroid-Associated Orbitopathy

Cited by 8 publications

References 20 publications

Metabolic features of orbital adipose tissue in patients with thyroid eye disease

Metabolic features of orbital adipose tissue in patients with thyroid eye disease

Tears as a Source of Biomarkers in the Diagnosis of Graves’ Orbitopathy

Tear-derived exosomal biomarkers of Graves’ ophthalmopathy

Contact Info

Product

Resources

About