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Biomolecules
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Biomarkers of Ocular Allergy and Dry Eye Disease
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Biomarkers of Ocular Allergy and Dry Eye Disease

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Biomarkers".

Deadline for manuscript submissions: closed (31 January 2024) | Viewed by 9040

Special Issue Editor

Dr. Anat Galor

E-Mail Website
Guest Editor
Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL 33136, USA
Interests: dry eye disease; dry eye; aqueous tear deficiency; evaporative deficiency; ocular surface inflammation; tear osmolarity; epidemiology

Special Issue Information

Dear Colleagues,

Dry eye disease (DED) is a heterogenous disease that can present with a variety of symptoms (e.g., dryness, burning, foreign body sensation, visual fluctuations) and signs (e.g., low tear production, unstable tear film, ocular surface inflammation, epithelial disruption. Underlying this heterogeneity is a complex pathophysiology which can include both tear and nerve abnormalities. Furthermore, DED can occur as an isolated phenomenon or secondary to a systemic disorder, such as Sjögren's syndrome or graft versus host disease. Ocular allergy is likewise heterogenous, and can occur in a seasonal or perennial pattern. Its pathophysiology can involve abnormalities in soluble and/or cellular components of the immune system. Like DED, it can be isolated to the ocular surface or associated with systemic conditions such as atopic dermatitis or asthma. Given these complexities, prognostic and diagnostic biomarkers are needed for both DED and ocular allergy to identify disease contributors that can be manipulated to deliver precision therapy to patients. This Special Issue will focus on this need and include original papers and reviews that discuss the state of the art of biomarkers for these two common ocular surface disorders.

Dr. Anat Galor
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. Biomolecules is an international peer-reviewed open access monthly 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 2700 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

  • ocular allergy
  • dry eye disease
  • Sjögren's syndrome
  • biomarker
  • prognostic biomarkers
  • diagnostic biomarkers

Published Papers (7 papers)

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Research

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14 pages, 1139 KiB  
Article
Role of Polyunsaturated Fatty Acids (PUFAs) and Eicosanoids on Dry Eye Symptoms and Signs
by Simran Mangwani-Mordani, Amanda Prislovsky, Daniel Stephenson, Charles E. Chalfant, Anat Galor and Nawajes Mandal
Biomolecules 2024, 14(3), 376; https://doi.org/10.3390/biom14030376 - 20 Mar 2024
Viewed by 761
Abstract
Polyunsaturated fatty acids (PUFAs) generate pro- and anti-inflammatory eicosanoids via three different metabolic pathways. This study profiled tear PUFAs and their metabolites and examined the relationships with dry eye (DE) and meibomian gland dysfunction (MGD) symptoms and signs. A total of 40 individuals [...] Read more.
Polyunsaturated fatty acids (PUFAs) generate pro- and anti-inflammatory eicosanoids via three different metabolic pathways. This study profiled tear PUFAs and their metabolites and examined the relationships with dry eye (DE) and meibomian gland dysfunction (MGD) symptoms and signs. A total of 40 individuals with normal eyelids and corneal anatomies were prospectively recruited. The symptoms and signs of DE and MGD were assessed, and tear samples (from the right eye) were analyzed by mass spectrometry. Mann–Whitney U tests assessed differences between medians; Spearman tests assessed correlations between continuous variables; and linear regression models assessed the impact of potential confounders. The median age was 63 years; 95% were male; 30% were White; and 85% were non-Hispanic. The symptoms of DE/MGD were not correlated with tear PUFAs and eicosanoids. DE signs (i.e., tear break-up time (TBUT) and Schirmer’s) negatively correlated with anti-inflammatory eicosanoids (11,12-dihydroxyeicosatrienoic acid (11,12 DHET) and 14,15-dihydroxyicosatrienoic acid (14,15, DHET)). Corneal staining positively correlated with the anti-inflammatory PUFA, docosahexaenoic acid (DHA). MGD signs significantly associated with the pro-inflammatory eicosanoid 15-hydroxyeicosatetranoic acid (15-HETE) and DHA. Several relationships remained significant when potential confounders were considered. DE/MGD signs relate more to tear PUFAs and eicosanoids than symptoms. Understanding the impact of PUFA-related metabolic pathways in DE/MGD may provide targets for new therapeutic interventions. Full article
(This article belongs to the Special Issue Biomarkers of Ocular Allergy and Dry Eye Disease)
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17 pages, 1940 KiB  
Article
Comparison of Transcriptomic Analysis of the Conjunctiva in Glaucoma-Treated Eyes with Dry Eyes and Healthy Controls
by Elena Carnero, Cristina Irigoyen-Bañegil, Itziar Gutiérrez, Leire Extramiana, Alfonso L. Sabater and Javier Moreno-Montañes
Biomolecules 2024, 14(1), 30; https://doi.org/10.3390/biom14010030 - 25 Dec 2023
Viewed by 901
Abstract
Ocular surface disease (OSD) associated with topical glaucoma drugs is a common issue impacting treatment adherence. We aimed to identify conjunctival transcriptomic changes in glaucoma and dry eye patients, comparing them to healthy controls. Bulbar conjunctival specimens were collected via impression cytology from [...] Read more.
Ocular surface disease (OSD) associated with topical glaucoma drugs is a common issue impacting treatment adherence. We aimed to identify conjunctival transcriptomic changes in glaucoma and dry eye patients, comparing them to healthy controls. Bulbar conjunctival specimens were collected via impression cytology from 33 patients treated for glaucoma, 9 patients with dry eye, and 14 healthy controls. RNA extraction and bulk RNA sequencing were performed, followed by bioinformatics analysis to detect gene dysregulation. Ingenuity pathways analysis (IPA) identified pathways and biological processes associated with these transcriptomic changes. Sequencing analysis revealed 200 modified genes in glaucoma patients compared to healthy individuals, 233 differentially expressed genes in dry eye patients versus controls, and 650 genes in treated versus dry eye samples. In glaucoma patients, 79% of altered pathways were related to host defense, while dry eye patients showed a 39% involvement of host response, 15% in cellular proliferation and integrity, and 16% of mitochondrial dysfunction. These findings were validated through qRT-PCR. Glaucoma patients showed an intensified conjunctival immune response as a potential cause of OSD, whereas in dry eye patients, in addition to the immune response, other mechanisms such as mitochondrial dysfunction or reduced cellular proliferation were observed. Full article
(This article belongs to the Special Issue Biomarkers of Ocular Allergy and Dry Eye Disease)
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13 pages, 1702 KiB  
Article
Dendritic Cell Density and Morphology Can Be Used to Differentiate Vernal Keratoconjunctivitis from Allergic Conjunctivitis
by Zahra Tajbakhsh, Blanka Golebiowski, Fiona Stapleton, Ramin Salouti, M. Hosein Nowroozzadeh, Mohammad Zamani, Nancy Briggs and Isabelle Jalbert
Biomolecules 2023, 13(10), 1469; https://doi.org/10.3390/biom13101469 - 29 Sep 2023
Viewed by 1035
Abstract
The aim of the study was to compare the distribution of corneal and conjunctival epithelial dendritic cells (DCs) in vernal keratoconjunctivitis (VKC), allergic conjunctivitis (AC), and non-allergic controls to examine if the allergy type causes differences in immune cell activation. The prospective study [...] Read more.
The aim of the study was to compare the distribution of corneal and conjunctival epithelial dendritic cells (DCs) in vernal keratoconjunctivitis (VKC), allergic conjunctivitis (AC), and non-allergic controls to examine if the allergy type causes differences in immune cell activation. The prospective study included 60 participants: 20 with VKC, 20 with AC, and 20 non-allergic controls. In vivo confocal microscopy was performed on the right eye. The locations scanned included the corneal centre, inferior whorl, corneal periphery, corneal limbus, and bulbar conjunctiva. The DCs were counted manually, and their morphology was assessed for the largest cell body size, the presence of dendrites, and the presence of long and thick dendrites. The DC density was higher in VKC and AC compared to non-allergic group at all locations (p ≤ 0.01) except at the inferior whorl. The DC density in VKC participants was significantly higher than in AC at the limbus (p < 0.001) but not at other locations. Both the AC and the VKC group had larger DC bodies at the corneal periphery and limbus compared to the non-allergic group (p ≤ 0.03). The study found a higher proportion of participants with DCs exhibiting long dendrites at both the corneal periphery in AC (p = 0.01) and at the corneal centre, periphery, and limbus in VKC, compared to the non-allergic group (p ≤ 0.001). In conclusion, a higher DC density at the limbus may be a marker of more severe VKC. DCs with larger cell bodies and a greater proportion of participants with DCs displaying long dendrites can be potential markers to differentiate allergy from non-allergy, and more severe forms of allergy from milder forms. Full article
(This article belongs to the Special Issue Biomarkers of Ocular Allergy and Dry Eye Disease)
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10 pages, 532 KiB  
Article
Impact of Tumor Necrosis Factor Receptor 1 (TNFR1) Polymorphism on Dry Eye Disease
by Kelly Acuna, Anjalee Choudhary, Elyana Locatelli, Daniel A. Rodriguez, Eden R. Martin, Roy C. Levitt and Anat Galor
Biomolecules 2023, 13(2), 262; https://doi.org/10.3390/biom13020262 - 31 Jan 2023
Cited by 1 | Viewed by 1960
Abstract
The goal of the study was to examine whether a genetic polymorphism in tumor necrosis factor receptor 1 (TNFR1) gene impacted the dry eye disease (DED) phenotype and response to anti-inflammatory therapy. The prospective study included 328 individuals with various dry [...] Read more.
The goal of the study was to examine whether a genetic polymorphism in tumor necrosis factor receptor 1 (TNFR1) gene impacted the dry eye disease (DED) phenotype and response to anti-inflammatory therapy. The prospective study included 328 individuals with various dry eye (DE) symptoms and signs recruited from the Miami Veterans Hospital eye clinic between October 2013 and October 2017. The population underwent genetic profiling for a polymorphism within the TNFR1 gene (rs1800693 [TT, TC, CC]). The study examined the genotype distribution and relationships between the genotype, phenotype, and response to anti-inflammatory therapy. The mean age of the population was 61.7 ± 9.8 years. Here, 92% self-identified as male, 44% as White, and 21% as Hispanic; 13% (n = 42) of individuals had a CC genotype. DED symptoms and signs were similar across the three genotype groups. Thirty individuals (four with CC) were subsequently treated with an anti-inflammatory agent. There was a non-significant trend for individuals with CC genotype to have a partial or complete symptomatic response to treatment compared with the other two groups (100% for CC vs. 40% for TT and 36.4% for TC, p = 0.22). In conclusion, the presence of homozygosity of minor allele C (CC genotype) in a single nucleotide polymorphism (SNP) within TNFR1 was noted in a minority of individuals with various aspects of DED, but did not impact the DED phenotype. Our findings suggest that the current phenotyping strategies for DED are insufficient to identify underlying disease contributors, including potential genetic contributors. Full article
(This article belongs to the Special Issue Biomarkers of Ocular Allergy and Dry Eye Disease)
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Review

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16 pages, 921 KiB  
Review
Therapeutic Effects of Stimulating the Melanocortin Pathway in Regulating Ocular Inflammation and Cell Death
by Shudan Wang, Francesca Kahale, Amirreza Naderi, Pier Luigi Surico, Jia Yin, Thomas Dohlman, Yihe Chen and Reza Dana
Biomolecules 2024, 14(2), 169; https://doi.org/10.3390/biom14020169 - 31 Jan 2024
Cited by 1 | Viewed by 1110
Abstract
Alpha-melanocyte-stimulating hormone (α-MSH) and its binding receptors (the melanocortin receptors) play important roles in maintaining ocular tissue integrity and immune homeostasis. Particularly extensive studies have demonstrated the biological functions of α-MSH in both immunoregulation and cyto-protection. This review summarizes the current knowledge of [...] Read more.
Alpha-melanocyte-stimulating hormone (α-MSH) and its binding receptors (the melanocortin receptors) play important roles in maintaining ocular tissue integrity and immune homeostasis. Particularly extensive studies have demonstrated the biological functions of α-MSH in both immunoregulation and cyto-protection. This review summarizes the current knowledge of both the physiological and pathological roles of α-MSH and its receptors in the eye. We focus on recent developments in the biology of α-MSH and the relevant clinical implications in treating ocular diseases. Full article
(This article belongs to the Special Issue Biomarkers of Ocular Allergy and Dry Eye Disease)
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19 pages, 1730 KiB  
Review
Advances in Sjögren’s Syndrome Dry Eye Diagnostics: Biomarkers and Biomolecules beyond Clinical Symptoms
by Kevin Y. Wu, Olivia Serhan, Anne Faucher and Simon D. Tran
Biomolecules 2024, 14(1), 80; https://doi.org/10.3390/biom14010080 - 08 Jan 2024
Viewed by 1288
Abstract
Sjögren’s syndrome dry eye (SSDE) is a subset of Sjögren’s syndrome marked by dry eye symptoms that is distinct from non-Sjögren’s syndrome dry eye (NSSDE). As SSDE can lead to severe complications, its early detection is imperative. However, the differentiation between SSDE and [...] Read more.
Sjögren’s syndrome dry eye (SSDE) is a subset of Sjögren’s syndrome marked by dry eye symptoms that is distinct from non-Sjögren’s syndrome dry eye (NSSDE). As SSDE can lead to severe complications, its early detection is imperative. However, the differentiation between SSDE and NSSDE remains challenging due to overlapping clinical manifestations. This review endeavors to give a concise overview of the classification, pathophysiology, clinical features and presentation, ocular and systemic complications, clinical diagnosis, and management of SSDE. Despite advancements, limitations in current diagnostic methods underscore the need for novel diagnostic modalities. Thus, the current review examines various diagnostic biomarkers utilized for SSDE identification, encompassing serum, salivary, and tear analyses. Recent advancements in proteomic research and exosomal biomarkers offer promising diagnostic potential. Through a comprehensive literature review spanning from 2016 to 2023, we highlight molecular insights and advanced diagnostic modalities that have the potential to enhance our understanding and diagnosis of SSDE. Full article
(This article belongs to the Special Issue Biomarkers of Ocular Allergy and Dry Eye Disease)
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Other

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17 pages, 646 KiB  
Systematic Review
Molecular Biomarkers in Ocular Graft-versus-Host Disease: A Systematic Review
by Jerry Bohlen, Charlyn Gomez, Jason Zhou, Fernando Martinez Guasch, Caitlyn Wandvik and Sarah Brem Sunshine
Biomolecules 2024, 14(1), 102; https://doi.org/10.3390/biom14010102 - 12 Jan 2024
Viewed by 1206
Abstract
Ocular graft-versus-host disease (oGVHD) affects ~50% of post-stem cell transplant patients and is the only form of GVHD diagnosed without a biopsy. As it must be distinguished from other dry eye diseases, there is a need to identify oGVHD biomarkers to improve diagnosis [...] Read more.
Ocular graft-versus-host disease (oGVHD) affects ~50% of post-stem cell transplant patients and is the only form of GVHD diagnosed without a biopsy. As it must be distinguished from other dry eye diseases, there is a need to identify oGVHD biomarkers to improve diagnosis and treatment. We conducted a systematic review of 19 scholarly articles published from 2018 to 2023 including articles focused on adult patients diagnosed with oGVHD following allogeneic hematopoietic stem cell transplant and used biomarkers as the outcome measure. Articles that were not original investigations or were not published in English were excluded. These clinical investigations explored different molecular oGVHD biomarkers and were identified on 3 October 2023 from the Scopus, PubMed, and Embase databases by using search terms including ocular graft-versus-host disease, biomarkers, cytokines, proteomics, genomics, immune response, imaging techniques, and dry-eye-related key terms. The Newcastle–Ottawa scale for case–control studies was used to assess bias. From the 19 articles included, cytokine, proteomic, lipid, and leukocyte profiles were studied in tear film, as well as ocular surface microbiota and fluorescein staining. Our findings suggest that cytokine profiling is the most studied oGVHD biomarker. Additionally, variations correlating these biomarkers with disease state may lead to a more targeted diagnosis and therapeutic approach. Limitations include language bias, publication bias, and sampling bias, as well as a lack of appropriate controls for included studies. Full article
(This article belongs to the Special Issue Biomarkers of Ocular Allergy and Dry Eye Disease)
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