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Molecular Advances in Dry Eye Syndrome
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Molecular Advances in Dry Eye Syndrome

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: 20 June 2025 | Viewed by 6716

Special Issue Editors

Prof. Dr. Maria Jesus Giráldez-Fernández

E-Mail Website
Guest Editor
1. Optometry Area, Department of Applied Physics, Faculty of Optics and Optometry, Optometry Clinic, Research Group GI 2092-Optometry, Universidade de Santiago de Compostela, Santiago de Compostela, Spain
2. Institute of Health Research of Santiago de Compostela (AC24-Group), University of Santiago de Compostela, Santiago de Compostela, Spain
Interests: optometry; dry eye disease; ocular surface; contact lens; tear substitutes; myopia; ophthalmic instrumentation
Special Issues, Collections and Topics in MDPI journals
Dr. Anxo Fernández Ferreiro

E-Mail Website
Guest Editor
Clinical Pharmacology Group, Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain
Interests: ocular drug delivery; ocular pharmacokinetic; drug development; pharmacogenetics; clinical and translational research
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Dry eye disease (DED) is a common ocular surface disease affecting a significant percentage of the population. Caused by tear film homeostasis disruption, DED is characterized by dryness, inflammation, discomfort, and visual disturbances. This condition greatly affects the quality of life of patients, and can potentially lead to permanent vision loss.

The purpose of this Special Issue is to report recent molecular advances in DED to assist in developing a better knowledge of DED-related pathophysiological mechanisms, diagnostic methods, and therapeutic approaches.

Potential topics include, but are not limited to, both immune and adaptive immune responses, ocular surface signs and symptoms, diagnostic methods, new pharmacological treatments, and specialized drug delivery systems.

Dr. Maria Jesus Giráldez-Fernández
Dr. Anxo Fernández Ferreiro
Guest Editors

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • dry eye disease
  • tear film osmolarity
  • tear film
  • artificial tear substitutes
  • biological tear substitutes
  • tear fluid biomarkers
  • tear film lipid layer
  • meibomian gland dysfunction
  • evaporative dry eye
  • aqueous deficiency dry eye
  • ocular surface inflammation
  • cytokines
  • histological analysis
  • pharmacological treatment

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Published Papers (4 papers)

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Research

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16 pages, 3484 KiB  
Article
Exosomes from Limosilactobacillus fermentum Ameliorate Benzalkonium Chloride-Induced Inflammation in Conjunctival Cells
by Kippeum Lee, Hyeonjun Gwon, Joo Yun Kim, Jae Jung Shim and Jae Hwan Lee
Int. J. Mol. Sci. 2024, 25(22), 12282; https://doi.org/10.3390/ijms252212282 - 15 Nov 2024
Cited by 1 | Viewed by 1386
Abstract
Dry eye is characterized by persistent instability and decreased tear production, which are accompanied by epithelial lesions and inflammation on the surface of the eye. In our previous paper, we reported that supplementation with Limosilactobacillus fermentum HY7302 (HY7302) could inhibit corneal damage in [...] Read more.
Dry eye is characterized by persistent instability and decreased tear production, which are accompanied by epithelial lesions and inflammation on the surface of the eye. In our previous paper, we reported that supplementation with Limosilactobacillus fermentum HY7302 (HY7302) could inhibit corneal damage in a benzalkonium chloride (BAC)-induced mouse model of dry eye, through its effects in gut microbiome regulation. The aim of this study was to determine what functional extracellular substances can alter the inflammatory response of conjunctival cells. We isolated exosomes from HY7302 probiotic culture supernatant, analyzed their morphological characteristics, and found that their average size was 143.8 ± 1.1 nm, which was smaller than the exosomes from the L. fermentum KCTC 3112 strain. In addition, HY7302-derived exosomes significantly reduced the levels of genes encoding pro-inflammatory cytokines, including interleukin (IL)-20, IL-8, IL-6, and IL-1B, in BAC-treated human conjunctival cells. Moreover, HY7302-derived exosomes significantly increased the levels of genes encoding tight junction proteins, including TJP1, TJP2, and occludin-1, in Caco-2 cells. Lastly, the HY7302 exosomes reduced mRNA expression levels of IL1B, IL20, IL6, IL8, and NFAT5 in a transwell coculture system. Our findings indicate that HY7302 exosomes have potential for use in the treatment of ocular inflammation-related dry eye disease, through gut–eye axis communication via exosomes. Full article
(This article belongs to the Special Issue Molecular Advances in Dry Eye Syndrome)
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14 pages, 1125 KiB  
Article
Clinical Effectiveness, Safety, and Compliance of Two Compounded Formulations of Tacrolimus Eye Drops: An Open-Label, Sequential Prospective Study
by María Puente-Iglesias, Andrea Cuartero-Martínez, Rosario Touriño-Peralba, María Teresa Rodríguez-Ares, María Jesús Giráldez, Eva Yebra-Pimentel, Laura García-Quintanilla, Xurxo García-Otero, Miguel González-Barcia, Irene Zarra-Ferro, Francisco J. Otero-Espinar, Anxo Fernández-Ferreiro and Ana Castro-Balado
Int. J. Mol. Sci. 2024, 25(18), 9847; https://doi.org/10.3390/ijms25189847 - 12 Sep 2024
Viewed by 1667
Abstract
Ophthalmic tacrolimus compounded formulations are usually made from the commercial intravenous presentation, which contains ethanol as a solubilizer due to the low solubility of tacrolimus. The use of cyclodextrins is presented as an alternative to ethanol, an ocular irritant excipient, to avoid its [...] Read more.
Ophthalmic tacrolimus compounded formulations are usually made from the commercial intravenous presentation, which contains ethanol as a solubilizer due to the low solubility of tacrolimus. The use of cyclodextrins is presented as an alternative to ethanol, an ocular irritant excipient, to avoid its long-term irritant effects. Open-label, sequential, prospective study to compare effectiveness, safety, and adherence of a new formulation of 0.015% tacrolimus with cyclodextrins (TCD) versus 0.03% tacrolimus with ethanol (TE). The ocular evaluation was assessed by ocular signs, corneal staining, subjective questionnaires as Visual Function Questionnaire (VFQ-25) and Visual Analogue Scale (VAS) of symptoms, lacrimal stability, ocular redness, and intraocular pressure. Compliance was assessed by VAS of adherence and empirically (difference between theoretical and actual consumption). Clinical ocular signs and corneal staining score remained stable for most patients 3 months after switching formulations. The TCD formulation did not modify the tear stability and intraocular pressure of the treated patients compared to the TE formulation. TCD eye drops significantly decreased the subjective pain values on VFQ-25 scale and burning sensation on the VAS symptom scale in comparison to TE formulation after 3 months after the change to TCD formulation. The novel tacrolimus in cyclodextrins formulation is a promising alternative for treating inflammatory ocular pathologies refractory to first-line treatments. Full article
(This article belongs to the Special Issue Molecular Advances in Dry Eye Syndrome)
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17 pages, 11790 KiB  
Article
Meibum Lipidomic Analysis in Evaporative Dry Eye Subjects
by Jacobo Garcia-Queiruga, Hugo Pena-Verdeal, Belen Sabucedo-Villamarin, Monica Paz-Tarrio, Esteban Guitian-Fernandez, Carlos Garcia-Resua, Eva Yebra-Pimentel and Maria J. Giraldez
Int. J. Mol. Sci. 2024, 25(9), 4782; https://doi.org/10.3390/ijms25094782 - 27 Apr 2024
Viewed by 2230
Abstract
Meibomian Glands (MG) are sebaceous glands responsible for the production of meibum, the main component of the Tear Film Lipid Layer (TFLL). The TFLL facilitates the spread of the tear film over the ocular surface, provides stability and reduces tear evaporation. Alterations in [...] Read more.
Meibomian Glands (MG) are sebaceous glands responsible for the production of meibum, the main component of the Tear Film Lipid Layer (TFLL). The TFLL facilitates the spread of the tear film over the ocular surface, provides stability and reduces tear evaporation. Alterations in meibum composition lead to different ocular alterations like Meibomian Gland Dysfunction (MGD) and subsequent Evaporative Dry Eye (EDE). The aim of the present study was to investigate the composition and abundance of meibum lipids and their relationship with eyelid margin abnormalities, lipid layer patterns and MG status. The study utilizes a lipidomic approach to identify and quantify lipids in meibum samples using an Elute UHPLC system. This system considered all four dimensions (mass/charge, retention time, ion mobility and intensity) to provide the accurate identification of lipid species. Samples were categorized as healthy or low/no signs of alteration (group 1) or severe signs of alteration or EDE/MGD (group 2). The current investigation found differences in Variable Importance in Projection lipid abundance between both groups for the MGD signs studied. Changes in meibum composition occur and are related to higher scores in eyelid margin hyperaemia, eyelid margin irregularity, MG orifice plugging, MG loss and lipid layer pattern. Full article
(This article belongs to the Special Issue Molecular Advances in Dry Eye Syndrome)
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Review

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27 pages, 2397 KiB  
Review
Sex Differences in the Lacrimal Gland: Implications for Dry Eye Disease
by Snježana Kaštelan, Koraljka Hat, Zora Tomić, Tomislav Matejić and Nikola Gotovac
Int. J. Mol. Sci. 2025, 26(8), 3833; https://doi.org/10.3390/ijms26083833 - 18 Apr 2025
Viewed by 759
Abstract
Sexual dimorphism significantly impacts the lacrimal gland’s structure, function, and ageing processes, playing an important role in dry eye disease (DED) pathophysiology. This multifactorial disorder, characterised by tear film instability, inflammation, and visual impairment, disproportionately affects women, especially after menopause. It highlights the [...] Read more.
Sexual dimorphism significantly impacts the lacrimal gland’s structure, function, and ageing processes, playing an important role in dry eye disease (DED) pathophysiology. This multifactorial disorder, characterised by tear film instability, inflammation, and visual impairment, disproportionately affects women, especially after menopause. It highlights the interplay between sex steroid hormones, lacrimal gland function, and environmental factors. Systemic and local androgens are vital for maintaining lacrimal gland health and tear production, while the role of oestrogens remains less clear. Evidence suggests dose and context-dependent effects on inflammation and glandular function. Histopathological and molecular studies reveal significant sex differences in the lacrimal gland, with women exhibiting more pronounced age-related degenerative changes, including fibrosis and acinar atrophy, contributing to their increased susceptibility to DED. Despite these findings, the underlying mechanisms connecting sex steroid hormones, receptor expression, and local tissue regulation to these disparities remain poorly understood, highlighting the need for further research. This review synthesises the current knowledge of sex-specific differences in the lacrimal gland, emphasising the importance of integrating systemic and local biomarkers, histological data, and molecular insights into personalised therapeutic strategies. By tailoring treatments to patients’ unique hormonal and molecular profiles, personalised medicine has the potential to transform DED management, addressing unmet clinical needs and improving outcomes. Full article
(This article belongs to the Special Issue Molecular Advances in Dry Eye Syndrome)
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