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Dry Eye and Ocular Surface Disorders, 5th Edition
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Dry Eye and Ocular Surface Disorders, 5th Edition

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 July 2024) | Viewed by 11254

Special Issue Editors

Dr. Murat Dogru

E-Mail Website
Guest Editor
Department of Ophthalmology, Keio University School of Medicine, Shi-nanomachi 35, Shinjuku-ku, Tokyo 160-8582, Japan
Interests: dry eye; oxidative stress; diagnostic imaging; biomarkers; ocular allergy; contact lens
Special Issues, Collections and Topics in MDPI journals
Dr. Takashi Kojima

E-Mail Website
Guest Editor
Department of Ophthalmology, School of Medicine, Keio University, Tokyo 160-8582, Japan
Interests: dry eye; neuropathic pain; refractive surgery; oxidative stress; behavior science
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In recent years, dry eye has been widely investigated in many studies, including epidemiological, basic, and clinical studies, and recent achievements in this field of study are remarkable. Dry eye is a disease in which tear film stability decreases. This mechanism is associated with inflammation, friction in the eyelids, changes in tear osmolarity, amount of tear secretion, wettability of the ocular surface, tear evaporation, etc., which interact in a complex way in the onset of pathological conditions. In addition, in dry eye disease, it was found that there was a difference between subjective symptoms and ocular findings. Recently, research was conducted that considered several elements, including the involvement of the nervous system, and it has become clear that dry eye also contains elements of neuropathic pain. Treatments that target tear stability, inflammation, and friction are often performed. Moreover, in recent years, a secretagogue made up of water and mucin components has been widely used in Asian countries. However, the understanding of dry eye pathology, diagnosis, and treatment is still inadequate. New insights and breakthroughs will be needed to overcome these problems in the future. In this Special Issue, we seek important research findings, including new findings in the fields of ocular surface and dry eye disease. Our aim is to broaden the direction and possibilities of dry eye research. We are very much looking forward to receiving your invaluable submissions to this Special Issue.

Dr. Murat Dogru
Dr. Takashi Kojima
Guest Editors

Manuscript Submission Information

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Keywords

  • dry eye
  • basic research
  • treatment animal model
  • neuropathic pain
  • ocular surface pathophysiology
  • diagnosis

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Published Papers (7 papers)

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Research

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9 pages, 4305 KiB  
Article
Granzyme B Expression in Conjunctiva of Patients with Pterygium
by Yoojin Choi, Isa Samad, Harshini Chakravarthy, Joanne Matsubara, David J. Granville and Sonia N. Yeung
Int. J. Mol. Sci. 2024, 25(16), 8679; https://doi.org/10.3390/ijms25168679 - 9 Aug 2024
Viewed by 646
Abstract
Pterygium is often associated with chronic ultraviolet (UV) radiation exposure and characterized by the overgrowth of conjunctiva and extracellular matrix (ECM) remodeling. Notably, several studies in the skin have demonstrated that chronic UV radiation can upregulate Granzyme B (GrB) expression and increase ECM [...] Read more.
Pterygium is often associated with chronic ultraviolet (UV) radiation exposure and characterized by the overgrowth of conjunctiva and extracellular matrix (ECM) remodeling. Notably, several studies in the skin have demonstrated that chronic UV radiation can upregulate Granzyme B (GrB) expression and increase ECM degradation. The aim of this study was to compare GrB expression between pterygium and healthy controls and to further link this GrB expression to mast cells. Post-mortem pterygium tissues and conjunctival tissues from age-matched controls were used to assess GrB expression via immunofluorescence and microscopy. We found a significantly higher density of GrB+ cells from pterygium specimens compared to healthy controls. Furthermore, many of the GrB+ cells in pterygium specimens co-expressed tryptase, a mast cell marker. These findings suggest a role for conjunctival mast cell-secreted GrB in the pathogenesis of pterygium and highlight GrB as a possible therapeutic target in delaying or halting pterygium progression. Full article
(This article belongs to the Special Issue Dry Eye and Ocular Surface Disorders, 5th Edition)
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15 pages, 3612 KiB  
Article
Exorbital Lacrimal Gland Ablation and Regrafting Induce Inflammation but Not Regeneration or Dry Eye
by Adriana de Andrade Batista Murashima, Ariane M. S. Sant’Ana, Jacqueline Ferreira Faustino-Barros, Elísio B. Machado Filho, Lilian Costa Mendes da Silva, Marina Zilio Fantucci, Carolina Maria Módulo, Fernando Chahud, Denny Marcos Garcia and Eduardo M. Rocha
Int. J. Mol. Sci. 2024, 25(15), 8318; https://doi.org/10.3390/ijms25158318 - 30 Jul 2024
Cited by 1 | Viewed by 804
Abstract
The study evaluated the regenerative responses of the lacrimal functional unit (LFU) after lacrimal gland (LG) ablation. The LG of Wistar rats was submitted to G1) partial LG ablation, G2) partial ablation and transplantation of an allogeneic LG, or G3) total LG ablation, [...] Read more.
The study evaluated the regenerative responses of the lacrimal functional unit (LFU) after lacrimal gland (LG) ablation. The LG of Wistar rats was submitted to G1) partial LG ablation, G2) partial ablation and transplantation of an allogeneic LG, or G3) total LG ablation, (n = 7–10/group). The eye wipe test, slit lamp image, tear flow, and histology were evaluated. RT-PCR analyzed inflammatory and proliferation mediators. The findings were compared to naïve controls after 1 and 2 months (M1 and M2). G3 presented increased corneal sensitivity, and the 3 groups showed corneal neovascularization. Histology revealed changes in the LG and corneal inflammation. In the LG, there was an increase in MMP-9 mRNA of G1 and G2 at M1 and M2, in RUNX-1 at M1 and M2 in G1, in RUNX-3 mRNA at M1 in G1, and at M2 in G2. TNF-α mRNA rose in the corneas of G1 and G2 at M2. There was an increase in the IL-1β mRNA in the trigeminal ganglion of G1 at M1. Without changes in tear flow or evidence of LG regeneration, LG ablation and grafting are unreliable models for dry eye or LG repair in rats. The surgical manipulation extended inflammation to the LFU. Full article
(This article belongs to the Special Issue Dry Eye and Ocular Surface Disorders, 5th Edition)
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8 pages, 1363 KiB  
Article
Eye Washing Downregulated Angiotensin-Converting Enzyme 2 in Conjunctival Tissue Samples from Smokers
by Hiroshi Fujishima, Hiroyuki Yazu, Eisuke Shimizu, Naoko Okada and Kazumi Fukagawa
Int. J. Mol. Sci. 2023, 24(24), 17526; https://doi.org/10.3390/ijms242417526 - 15 Dec 2023
Viewed by 920
Abstract
This study aimed to (1) determine whether the expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 is increased in tobacco smokers, which potentially increases their susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and (2) assess whether eye [...] Read more.
This study aimed to (1) determine whether the expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 is increased in tobacco smokers, which potentially increases their susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and (2) assess whether eye rinsing can reduce susceptibility. This prospective study included 20 eyes of 10 smokers and 18 eyes of nine healthy non-smokers (control) for reverse-transcription polymerase chain reaction. This study also included 28 eyes of 14 smokers and 16 eyes of eight healthy non-smokers (control) for enzyme-linked immunosorbent assay. Tear and impression cytology samples were collected from the right eye of each patient. The left eye was then rinsed for 30 s, and after 5 min, the tear and impression cytology samples were collected in the same manner. The expression of the ACE2 gene was significantly higher in the conjunctiva of smokers (n = 17; median 3.07 copies/ng of total RNA) than in those of non-smokers (n = 17; median 1.92 copies/ng of total RNA, p = 0.003). Further, mRNA expression and protein levels of ACE2 were weakly correlated in smokers (r = 0.49). ACE2 protein levels in Schirmer’s strip samples were significantly reduced from 5051 to 3202 pg/mL after eye washing (n = 10; p = 0.001). Ocular surface cells are susceptible to SARS-CoV-2 infection. Smoking may be a risk factor for SARS-CoV-2 infection, and eye rinsing may reduce the risk of infection. Full article
(This article belongs to the Special Issue Dry Eye and Ocular Surface Disorders, 5th Edition)
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12 pages, 6058 KiB  
Article
A Comprehensive Assessment of Tear-Film-Oriented Diagnosis (TFOD) in a Dacryoadenectomy Dry Eye Model
by Saki Sakakura, Emi Inagaki, Yuichiro Ochiai, Masatoshi Yamamoto, Naofumi Takai, Taeko Nagata, Kazunari Higa, Yasunori Sato, Hiroshi Toshida, Dogru Murat, Masatoshi Hirayama, Yoko Ogawa, Kazuno Negishi and Shigeto Shimmura
Int. J. Mol. Sci. 2023, 24(22), 16510; https://doi.org/10.3390/ijms242216510 - 20 Nov 2023
Viewed by 1694
Abstract
Tear film instability is a major cause of dry eye disease. In order to treat patients with short tear film breakup time (TBUT)-type dry eye, the development of tear film stabilizing agents is essential. However, the lack of an appropriate animal model of [...] Read more.
Tear film instability is a major cause of dry eye disease. In order to treat patients with short tear film breakup time (TBUT)-type dry eye, the development of tear film stabilizing agents is essential. However, the lack of an appropriate animal model of tear film instability has made drug development difficult. Although rabbit dry eye models have been reported in the past, there are only a few reports that focus on tear film instability. Herein, we assessed the tear film stability of a rabbit dry eye model induced by dacryoadenectomy. A clinical evaluation of the ocular surface, interferometry, and histological assessments of the cornea and conjunctiva were performed. Following the removal of the lacrimal glands, TBUT was shortened significantly, with dimple and random breakup patterns prominently observed. Furthermore, the blink rate in this model increased after dacryoadenectomy, suggesting that this model partially captured the phenotypes of human short TBUT-type dry eye and may be useful as an animal model for investigating potential drug candidates. Full article
(This article belongs to the Special Issue Dry Eye and Ocular Surface Disorders, 5th Edition)
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21 pages, 3446 KiB  
Article
Inflammation of Dry Eye Syndrome: A Cellular Study of the Epithelial and Macrophagic Involvement of NFAT5 and RAGE
by Fanny Henrioux, Valentin Navel, Corinne Belville, Coline Charnay, Audrey Antoine, Frédéric Chiambaretta, Vincent Sapin and Loïc Blanchon
Int. J. Mol. Sci. 2023, 24(13), 11052; https://doi.org/10.3390/ijms241311052 - 4 Jul 2023
Cited by 1 | Viewed by 2214
Abstract
Dry eye inflammation is a key step in a vicious circle and needs to be better understood in order to break it. The goals of this work were to, first, characterize alarmins and cytokines released by ocular surface cells in the hyperosmolar context [...] Read more.
Dry eye inflammation is a key step in a vicious circle and needs to be better understood in order to break it. The goals of this work were to, first, characterize alarmins and cytokines released by ocular surface cells in the hyperosmolar context and, second, study the role of NFAT5 in this process. Finally, we studied the potential action of these alarmins in ocular surface epithelial cells and macrophages via RAGE pathways. HCE and WKD cell lines were cultured in a NaCl-hyperosmolar medium and the expression of alarmins (S100A4, S100A8, S100A9, and HMGB1), cytokines (IL6, IL8, TNFα, and MCP1), and NFAT5 were assessed using RT-qPCR, ELISA and multiplex, Western blot, immunofluorescence, and luciferase assays. In selected experiments, an inhibitor of RAGE (RAP) or NFAT5 siRNAs were added before the hyperosmolar stimulations. HCE and WKD cells or macrophages were treated with recombinant proteins of alarmins (with or without RAP) and analyzed for cytokine expression and chemotaxis, respectively. Hyperosmolarity induced epithelial cell inflammation depending on cell type. NFAT5, but not RAGE or alarmins, participated in triggering epithelial inflammation. Furthermore, the release of alarmins induced macrophage migration through RAGE. These in vitro results suggest that NFAT5 and RAGE have a role in dry eye inflammation. Full article
(This article belongs to the Special Issue Dry Eye and Ocular Surface Disorders, 5th Edition)
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Review

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15 pages, 3245 KiB  
Review
Corneal Epithelial Changes in Diabetic Patients: A Review
by Lidia Ladea, Mihail Zemba, Maria Ioana Calancea, Mihai Valeriu Călțaru, Christiana Diana Maria Dragosloveanu, Ruxandra Coroleucă, Eduard Lucian Catrina, Iulian Brezean and Valentin Dinu
Int. J. Mol. Sci. 2024, 25(6), 3471; https://doi.org/10.3390/ijms25063471 - 19 Mar 2024
Cited by 1 | Viewed by 1855
Abstract
The relationship between diabetes mellitus and ocular complications has been extensively studied by many authors. Diabetic keratopathy has already been well characterized and defined as a clinical entity. This review focuses on exploring corneal epithelial changes in diabetic patients, aiming to provide a [...] Read more.
The relationship between diabetes mellitus and ocular complications has been extensively studied by many authors. Diabetic keratopathy has already been well characterized and defined as a clinical entity. This review focuses on exploring corneal epithelial changes in diabetic patients, aiming to provide a pragmatic overview of the existing knowledge on this topic. The paper systematically examines alterations in corneal epithelial structure and their impact on diabetic patients. Advanced imaging techniques are also discussed for their role in precise characterization and improved diagnostics. Additionally, the paper explores the mechanisms behind corneal epithelial changes in diabetes, looking at factors such as hyperglycemia, oxidative stress, and Advanced Glycation End-Products. The impact of altered corneal epithelial integrity on barrier function and susceptibility to external issues is considered, addressing potential links to heightened proteolytic enzyme activities and delayed wound healing observed in diabetic individuals. The review also covers the practical implications of corneal epithelial changes, including the association with corneal erosions, persistent epithelial defects, and an increased risk of dry eye syndrome in diabetic patients. Full article
(This article belongs to the Special Issue Dry Eye and Ocular Surface Disorders, 5th Edition)
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22 pages, 666 KiB  
Review
Impact of Exposomes on Ocular Surface Diseases
by Merrelynn Hong, Louis Tong, Jodhbir S. Mehta and Hon Shing Ong
Int. J. Mol. Sci. 2023, 24(14), 11273; https://doi.org/10.3390/ijms241411273 - 10 Jul 2023
Cited by 4 | Viewed by 2024
Abstract
Ocular surface diseases (OSDs) are significant causes of ocular morbidity, and are often associated with chronic inflammation, redness, irritation, discomfort, and pain. In severe OSDs, loss of vision can result from ocular surface failure, characterised by limbal stem cell deficiencies, corneal vascularisation, corneal [...] Read more.
Ocular surface diseases (OSDs) are significant causes of ocular morbidity, and are often associated with chronic inflammation, redness, irritation, discomfort, and pain. In severe OSDs, loss of vision can result from ocular surface failure, characterised by limbal stem cell deficiencies, corneal vascularisation, corneal opacification, and surface keratinisation. External and internal exposomes are measures of environmental factors that individuals are exposed to, and have been increasingly studied for their impact on ocular surface diseases. External exposomes consist of external environmental factors such as dust, pollution, and stress; internal exposomes consist of the surface microbiome, gut microflora, and oxidative stress. Concerning internal exposomes, alterations in the commensal ocular surface microbiome of patients with OSDs are increasingly reported due to advancements in metagenomics using next-generation sequencing. Changes in the microbiome may be a consequence of the underlying disease processes or may have a role in the pathogenesis of OSDs. Understanding the changes in the ocular surface microbiome and the impact of various other exposomes may also help to establish the causative factors underlying ocular surface inflammation and scarring, the hallmarks of OSDs. This review provides a summary of the current evidence on exposomes in various OSDs. Full article
(This article belongs to the Special Issue Dry Eye and Ocular Surface Disorders, 5th Edition)
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