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Applied Sciences
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Potential Biomarkers in Tears
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Potential Biomarkers in Tears

A special issue of Applied Sciences (ISSN 2076-3417). This special issue belongs to the section "Applied Biosciences and Bioengineering".

Deadline for manuscript submissions: closed (20 February 2022) | Viewed by 14201

Special Issue Editor

Dr. Amalia Enríquez-de-Salamanca

E-Mail Website
Guest Editor
1. Institute of Applied Ophthalmobiology (IOBA), University of Valladolid (UVa), Valladolid, Spain;
2. Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Zaragoza, Spain
Interests: My main research field is ocular surface inflammation, where I investigate the characterization of potential biomarkers (e.g., disease, activity, therapeutic), in tears and/or epithelial cells in immune-based chronic inflammatory diseases of the ocular surface, such as dry eye disease, chronic allergy (atopic keratoconjunctivits and vernal keratoconjunctivitis) and ocular chronic pain. My research also includes the study of the role of corneal and conjunctival epithelial cells for these diseases

Special Issue Information

Dear Colleagues,

We are pleased to invite you to submit papers regarding this Special Issue concerning the potential biomarkers in tears. The issue intends to deliver an overview of the current knowledge in this field by bringing together studies about potential biomarkers (e.g., diagnostic, response, predictive, prognostic, susceptibility, therapeutic) in tears and also about their application.

Tear biomarkers are playing an increasingly important role in the field of predictive, preventative and personalized medicine. Through proteomic, metabolomic, and lipidomic analysis, several molecules and/or panels of a combination of several of them have been pointed out as promising biomarkers in several ocular diseases, particularly in dry eye disease, but also in several others such as ocular chronic allergy, glaucoma, keratoconus, keratopathy, keratitis, trachoma, aniridia or uveitis among others. Additionally, biomarkers have proven their usefulness in systemic diseases such as diabetic retinopathy, systemic sclerosis, cystic fibrosis, cancer, or in neurological disorders such as multiple sclerosis or Parkinson’s disease. Tear biomarkers can serve as indicators of disease severity, activity or therapeutic response, and they are considered as good candidates to be used as objective evaluation endpoints for objective monitoring in clinical trials. They also increase the knowledge about the molecular mechanisms underlying diseases. Additionally, biomarkers in tears can be used to establish responsive profiles which may allow for the identification of patients with a predictable response or susceptibility to a given condition.

Dr. Amalia Enríquez-de-Salamanca
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Applied Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2400 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • tear fluid
  • biomarkers
  • proteomics
  • metabolomics
  • lipidomics
  • ocular surface inflammation
  • dry eye disease
  • ocular diseases
  • systemic diseases
  • eye
  • ocular
  • ophthalmology

Published Papers (6 papers)

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Editorial

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2 pages, 185 KiB  
Editorial
Special Issue on “Potential Biomarkers in Tears”
by Amalia Enríquez-de-Salamanca
Appl. Sci. 2022, 12(15), 7579; https://doi.org/10.3390/app12157579 - 28 Jul 2022
Viewed by 934
Abstract
Tear biomarkers play an increasingly important role in the field of predictive, preventive, and personalized medicine [...] Full article
(This article belongs to the Special Issue Potential Biomarkers in Tears)

Research

Jump to: Editorial

6 pages, 842 KiB  
Article
Strip Meniscometry Tube in the Assessment of Tear Lactoferrin in Non-Obese Diabetic (NOD) Mice
by Murat Dogru, Takashi Kojima, Taeko Nagata and Kazuo Tsubota
Appl. Sci. 2022, 12(7), 3700; https://doi.org/10.3390/app12073700 - 06 Apr 2022
Cited by 1 | Viewed by 1348
Abstract
Purpose: To investigate the applicability of strip meniscometry tube (SMT) in the measurement of tear lactoferrin in non-obese diabetic mice (NOD). Methods: SMT (SMTube, Echo Electricity Co., Ltd., Tokyo, Japan) and fluorescein staining tests were performed on 7–14 week NOD- male mice ( [...] Read more.
Purpose: To investigate the applicability of strip meniscometry tube (SMT) in the measurement of tear lactoferrin in non-obese diabetic mice (NOD). Methods: SMT (SMTube, Echo Electricity Co., Ltd., Tokyo, Japan) and fluorescein staining tests were performed on 7–14 week NOD- male mice (n = 4) and age and sex matched wild–type (Balbc, WT) mice (n = 5). Tears collected during SMT underwent lactoferrin concentration measurement by ELISA. Results: The mean SMT value was significantly lower in NOD mice compared to wild-type mice (p = 0.01). The mean corneal fluorescein staining score in the NOD mice was significantly lower compared with the wild-type mice (p = 0.03). The mean tear lactoferrin level also showed a significantly lower concentration in NOD mice (p = 0.02). Conclusions: SMT has been shown to be an effective tool in measuring tear volume in humans, cats, dogs, and mice. SMT may also serve as a useful tool for tear lactoferrin assessment in NOD and WT mice in experimental settings. Full article
(This article belongs to the Special Issue Potential Biomarkers in Tears)
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8 pages, 1033 KiB  
Communication
Tears as the Next Diagnostic Biofluid: A Comparative Study between Ocular Fluid and Blood
by Prashanth Ravishankar and Anna Daily
Appl. Sci. 2022, 12(6), 2884; https://doi.org/10.3390/app12062884 - 11 Mar 2022
Cited by 11 | Viewed by 4996
Abstract
The need to easily isolate small molecular weight proteins and genomic fragments has prompted a search for an alternative biofluid to blood that has traversed sweat, urine, saliva, and even breath. In this study, both the genomic and proteomic profiles of tears and [...] Read more.
The need to easily isolate small molecular weight proteins and genomic fragments has prompted a search for an alternative biofluid to blood that has traversed sweat, urine, saliva, and even breath. In this study, both the genomic and proteomic profiles of tears and blood are evaluated to determine the similarity and differences between the two biofluids. Both fluids were tested utilizing microarray panels for identifying proteins as well as isolation of microRNA for sequencing. As anticipated, most (118) of the proteins detected in plasma were also detected in the tear samples, with tear samples also showing 34 unique proteins that were not found in the plasma. Over 400 microRNAs were isolated in both samples with 250 microRNA fragments commonly expressed in both tears and blood. This preliminary analysis, along with simplicity of collection and processing, lends credence to further investigate tears as an alternative biofluid to blood. Full article
(This article belongs to the Special Issue Potential Biomarkers in Tears)
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49 pages, 4160 KiB  
Article
Age- and Sex-Adjusted Reference Intervals in Tear Cytokine Levels in Healthy Subjects
by Itziar Fernández, Amalia Enríquez-de-Salamanca, Alejandro Portero, Carmen García-Vázquez, Margarita Calonge and José M. Herreras
Appl. Sci. 2021, 11(19), 8958; https://doi.org/10.3390/app11198958 - 26 Sep 2021
Cited by 1 | Viewed by 1599
Abstract
Alterations in tear cytokine levels have been associated with various ocular disorders as compared to those in healthy subjects. However, age and sex are not always considered in these comparisons. In this study we aimed to establish age and sex reference intervals (RIs) [...] Read more.
Alterations in tear cytokine levels have been associated with various ocular disorders as compared to those in healthy subjects. However, age and sex are not always considered in these comparisons. In this study we aimed to establish age and sex reference intervals (RIs) for tear cytokine levels in healthy people. Tear samples were taken from 75 males and 82 females, aged 18–88 years, and tear cytokine levels were determined. Age- and sex-adjusted RIs for epidermal growth factor (EGF), fractalkine, interleukin (IL)-1 receptor antagonist (RA), IL-7, IL-8, interferon inducible protein (IP)-10, monocyte chemotactic protein (MCP)-1, and vascular endothelial growth factor (VEGF) tear cytokine levels in a healthy sample were established using generalized additive for location, scale and shape (GAMLSS) models. RIs were tested in two external samples: a validation sample of 40 individuals with normal results at four Dry Eye Disease (DED) clinical diagnostic tests (OSDI, T-BUT, corneal staining and Schirmer test); and a utility sample of 13 severe DED cases. IL-1RA, IL-8, IP-10, and MCP-1 levels showed a positive association with age, while EGF was negatively correlated. IL-7 concentration increased up to 40 years and again after 70 years, observing a quasi-linear decrease between them. For VEGF, higher levels were observed in the middle-aged range. Regarding sex-influence, fractalkine tear levels were higher in men, whereas those of IL-7, IL-8, and IP-10 were higher in women. Using the estimated age- and sex-adjusted RIs, more than 92% of the validation sample was correctly classified, and 100% of the severe DED patients in the utility sample had concentrations outside the RIs in at least two of the cytokines evaluated. Full article
(This article belongs to the Special Issue Potential Biomarkers in Tears)
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12 pages, 1278 KiB  
Article
Longitudinal Tear Protein Changes Correlate with Ocular Chronic GVHD Development in Allogeneic Hematopoietic Stem Cell Transplant Patients
by Carmen Ciavarella, Gloria Astolfi, Nicola Valsecchi, Francesco Barbato, Mario Arpinati, Francesca Bonifazi and Piera Versura
Appl. Sci. 2021, 11(17), 8221; https://doi.org/10.3390/app11178221 - 04 Sep 2021
Cited by 2 | Viewed by 1579
Abstract
Ocular graft-versus-host disease (oGVHD) is a manifestation of chronic GVHD, frequently occurring in patients after allogeneic hematopoietic stem cell transplant (HSCT). We analyzed tear protein changes before and after allogeneic HSCT, and correlated their levels with the oGVHD development. This retrospective study included [...] Read more.
Ocular graft-versus-host disease (oGVHD) is a manifestation of chronic GVHD, frequently occurring in patients after allogeneic hematopoietic stem cell transplant (HSCT). We analyzed tear protein changes before and after allogeneic HSCT, and correlated their levels with the oGVHD development. This retrospective study included 102 patients, and data were recorded before the conditioning treatment, and after 3 to 6 months postoperatively. Tear protein analysis was performed with the Agilent-2100 Bioanalyzer on individual tears sampled by aspiration. Total protein (TP), Lysozyme-C (LYS-C), Lactoferrin (LACTO), Lipocalin-1 (LIPOC-1), Transferrin (TRANSF), Albumin (ALB), and Zinc-alpha-2-glycoprotein (ZAG-2) levels were retrieved and statistically analyzed. Following HSCT forty-three patients developed oGVHD. TP, LACTO, LYS-C, and ZAG-2 levels significantly decreased post-HSCT as compared to pre HSCT levels. In univariate analysis, TP, LACTO, and ZAG-2 decrease was associated with an increased development of oGVHD (OR = 4.49; 95% CI, 1.9 to 10.5; p < 0.001; OR = 3.08; 95% CI 1.3 to 7.6; p = 0.01; OR = 11.1; 95% CI 2.7 to 46.6; p < 0.001, respectively). TRANSF post-HSCT levels significantly increased (OR 15.7; 95% CI, 4.1 to 52.2; p = 0.0001). No pre-post-HSCT changes were shown in ALB and LIPOC-1 levels. Data suggest that TP content, LACTO, TRANSF, and ZAG-2 pre-post changes might be significant predictors of oGVHD development. Full article
(This article belongs to the Special Issue Potential Biomarkers in Tears)
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13 pages, 879 KiB  
Article
A Pilot Proteomic Study of Normal Human Tears: Leptin as a Potential Biomarker of Metabolic Disorders
by Mungunshur Byambajav, Cristina Arroyo-del Arroyo, Amalia Enríquez-de-Salamanca, Itziar Fernández, Eilidh Martin and Suzanne Hagan
Appl. Sci. 2021, 11(12), 5755; https://doi.org/10.3390/app11125755 - 21 Jun 2021
Cited by 3 | Viewed by 2351
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Potential Biomarkers in Tears)
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