scholarly journals A Pilot Proteomic Study of Normal Human Tears: Leptin as a Potential Biomarker of Metabolic Disorders

2021 ◽  
Vol 11 (12) ◽  
pp. 5755
Author(s):  
Mungunshur Byambajav ◽  
Cristina Arroyo-del Arroyo ◽  
Amalia Enríquez-de-Salamanca ◽  
Itziar Fernández ◽  
Eilidh Martin ◽  
...  

The concentrations of insulin, leptin, active ghrelin, C-peptide and gastric inhibitory polypeptide (GIP) and their inter-day variations were examined in normal human tears. In addition, correlations between the concentrations of these metabolic proteins and ocular surface parameters were determined. Subjects with healthy ocular surfaces attended three visits, with 7-day intervals. Tear evaporation rate (TER) and non-invasive tear break-up time (NITBUT) were assessed, and a total of 2 µL tears were collected from all subjects. Tear fluid concentrations of insulin, leptin, active ghrelin, C-peptide and GIP were measured by multiplex bead analysis. Insulin was the most highly expressed metabolic protein, followed by leptin, C-peptide, active ghrelin and GIP. Of these, only active ghrelin had a significant inter-day variation (p < 0.05). There was no inter-day variation in the mean concentrations of the other metabolic proteins. Leptin had a strong intra-class reproducibility. No correlation was detected between tear metabolic protein concentrations and ocular surface parameters. This pilot study shows, for the first time, that active ghrelin and GIP are detectable in healthy tears. The strong intra-class reproducibility for leptin shows that it could be used as a potential tear fluid biomarker and, possibly, in determining the effects of metabolic disorders on the ocular surface.

Author(s):  
Jon Roger Eidet ◽  
Maja Akopian ◽  
Ole K. Olstad ◽  
Øystein Kalsnes Jørstad ◽  
Morten C. Moe ◽  
...  

Abstract Background To identify candidate tear fluid biomarkers in patients with unilateral acute anterior uveitis (AAU) that can aid in the differentiation between these patients and patients with bacterial keratitis or healthy controls. Methods Thirteen patients (40.1 ± 16.2 years of age) with unilateral AAU, seven patients with unilateral bacterial keratitis (40.2 ± 15.3 years of age), and 14 healthy subjects (41.1 ± 11.6 years of age) were included. The tear proteome of affected eyes was compared with that of the unaffected eye or healthy controls. Proteins were identified by liquid chromatography tandem mass spectrometry and enzyme-linked immunosorbent assay. Results Relative protein ratios were detected and calculated for 272 unique proteins. Compared with healthy controls and the unaffected eye, the top upregulated proteins in AAU eyes were submaxillary gland androgen regulated protein 3B (SMR3B) and SMR3A. Similarly, the top upregulated proteins in bacterial keratitis were S100 calcium-binding protein A9 and orosomucoid 2. The acute phase response protein Serpin Family A Member 3 (SERPINA3) was increased in the healthy eye of AAU patients (P = 0.019) compared with healthy controls. Laser flare measurements in affected eyes of AAU patients showed positive logarithmic correlation with SERPINA3 in tear samples of the unaffected eye (P = 0.022). The use of SERPINA3 as a tear biomarker yielded a sensitivity of 85% and a specificity of 71% in detecting patients with AAU in the study population. Conclusions The acute phase response protein SERPINA3 was increased in tear samples of unaffected eyes of patients with unilateral AAU compared with healthy controls. This study highlights SERPINA3 as a potential biomarker for AAU. Future research should explore the dynamic properties of SERPINA3 in the tear fluid of active and quiescent uveitis eyes.


Diagnostics ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 71
Author(s):  
Yong-Soo Byun ◽  
Hyun Jung Lee ◽  
Soojung Shin ◽  
Moon Young Choi ◽  
Hyung-Seung Kim ◽  
...  

Autophagy has been suggested to have an important role in the pathogenesis of Sjögren syndrome (SS). We previously identified that autophagy related 5 (ATG5) was elevated in the tear and conjunctival epithelial cells of SS dry eyes (DE) compared to non-SS DE. The purpose of this study was to investigate the role of tear ATG5 as a potential biomarker in the diagnosis of SS. To confirm this hypothesis, we evaluated the tear ATG5 concentration, and other ocular tests (Schirmer I, tear breakup time (TBUT), ocular surface staining (OSS) score, ocular surface disease index (OSDI)) in SS and non-DE, and compared their diagnostic performance to discriminate SS from non-SS DE. Tear ATG5 showed the greatest area under the curve (AUC = 0.984; 95% CI, 0.930 to 0.999) among the tests, and a 94.6% sensitivity and 93.6% specificity at a cutoff value of >4.0 ng/mL/μg. Our data demonstrated that tear ATG5 may be helpful as an ocular biomarker to diagnose and assess SS. In the future, the diagnostic power of tear ATG for SS should be validated.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Aidan Kenny ◽  
Eva M. Jiménez-Mateos ◽  
María Ascensión Zea-Sevilla ◽  
Alberto Rábano ◽  
Pablo Gili-Manzanaro ◽  
...  

Abstract Alzheimer’s disease (AD) is characterized by a progressive loss of neurons and cognitive functions. Therefore, early diagnosis of AD is critical. The development of practical and non-invasive diagnostic tests for AD remains, however, an unmet need. In the present proof-of-concept study we investigated tear fluid as a novel source of disease-specific protein and microRNA-based biomarkers for AD development using samples from patients with mild cognitive impairment (MCI) and AD. Tear protein content was evaluated via liquid chromatography-mass spectrometry and microRNA content was profiled using a genome-wide high-throughput PCR-based platform. These complementary approaches identified enrichment of specific proteins and microRNAs in tear fluid of AD patients. In particular, we identified elongation initiation factor 4E (eIF4E) as a unique protein present only in AD samples. Total microRNA abundance was found to be higher in tears from AD patients. Among individual microRNAs, microRNA-200b-5p was identified as a potential biomarker for AD with elevated levels present in AD tear fluid samples compared to controls. Our study suggests that tears may be a useful novel source of biomarkers for AD and that the identification and verification of biomarkers within tears may allow for the development of a non-invasive and cost-effective diagnostic test for AD.


1989 ◽  
Vol 416 (1) ◽  
pp. 19-23 ◽  
Author(s):  
Moshe Kalina ◽  
Lars Grimelius ◽  
Bjorn Cedermark ◽  
Ilan Hammel

Author(s):  
R Garaa ◽  
F Norris ◽  
J Wright ◽  
L Morgan ◽  
S Hampton ◽  
...  

We investigated the contributions made by the entero-insular axis, proinsulin and the fractional hepatic extraction of insulin to the hyperinsulinaemia characteristic of polycystic ovarian syndrome (PCOS). We measured plasma glucose, gastric inhibitory polypeptide (GIP), glucagon-like peptide-1 (7–36 amide) (GLP-17–36 amide), immunoreactive insulin (IRI), intact proinsulin (IPI), and C-peptide concentrations during a 75 g oral glucose tolerance test in seven normal weight women with PCOS and eight healthy women. Women with PCOS had higher fasting ( P = 0·05) and integrated ( P < 0·01) IRI concentrations than controls. Fasting C-peptide levels were similar in both groups but integrated C-peptide ( P < 0·05) concentrations were greater in PCOS subjects than controls. Fasting and integrated concentrations of glucose, GIP and GLP-17–36 amide were similar in subjects with PCOS and controls. Although fasting IPI concentrations were similar in both groups, integrated IPI concentrations were higher ( P = 0·05) in patients with PCOS. Women with PCOS had similar fasting but higher ( P <0·05) integrated IRI: C-peptide molar ratios than controls. Fasting and integrated IPI: IRI molar ratios were similar in both groups. These results confirm that lean women with PCOS have peripheral hyperinsulinaemia. The mild fasting hyperinsulinaemia is due to increased pancreatic secretion, whereas the stimulated hyperinsulinaemia is due to both pancreatic hypersecretion and reduced fractional hepatic extraction of insulin. Hyperproinsulinaemia is modest and appropriate in PCOS. GIP and GLP-17–36 amide do not contribute to the stimulated hyperinsulinaemia in PCOS.


2013 ◽  
Vol 23 (4) ◽  
pp. 488-495 ◽  
Author(s):  
Piera Versura ◽  
Vincenzo Profazio ◽  
Giuseppe Giannaccare ◽  
Michela Fresina ◽  
Emilio C. Campos

2019 ◽  
Vol 20 (19) ◽  
pp. 4674 ◽  
Author(s):  
Inger van Steenoven ◽  
Barbara Noli ◽  
Cristina Cocco ◽  
Gian-Luca Ferri ◽  
Patrick Oeckl ◽  
...  

In a previous proteomic study, we identified the neurosecretory protein VGF (VGF) as a potential biomarker for dementia with Lewy bodies (DLB). Here, we extended the study of VGF by comparing levels in cerebrospinal fluid (CSF) from 44 DLB patients, 20 Alzheimer’s disease (AD) patients, and 22 cognitively normal controls selected from the Amsterdam Dementia Cohort. CSF was analyzed using two orthogonal analytical methods: (1) In-house-developed quantitative ELISA and (2) selected reaction monitoring (SRM). We further addressed associations of VGF with other CSF biomarkers and cognition. VGF levels were lower in CSF from patients with DLB compared to either AD patients or controls. VGF was positively correlated with CSF tau and α-synuclein (0.55 < r < 0.75), but not with Aβ1-42. In DLB patients, low VGF levels were related to a more advanced cognitive decline at time of first presentation, whereas high levels of VGF were associated with steeper subsequent longitudinal cognitive decline. Hence, CSF VGF levels were lower in DLB compared to both AD and controls across different analytical methods. The strong associations with cognitive decline further points out VGF as a possible disease stage or prognostic marker for DLB.


2020 ◽  
Vol 46 (5) ◽  
pp. 291-296 ◽  
Author(s):  
Miki Mizuno ◽  
Motoko Kawashima ◽  
Miki Uchino ◽  
Natsume Suzuki ◽  
Hiroto Mitamura ◽  
...  

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