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Diseases of the Eye and Adnexa: From Cellular and Molecular Mechanisms to Novel Therapeutic Approaches

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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 December 2023) | Viewed by 12105

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Dr. Igor A. Butovich

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Department of Ophthalmology, and the Graduate School of Biomedical Sciences, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9057, USA
Interests: meibomian gland dysfunction; dry eye; lipidomics; mass spectrometry
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Special Issue Information

Dear Colleagues,

This Special Issue of IJMS is welcoming submissions that would provide new insights into the molecular aspects of physiology and biochemistry of the eye and adnexa, including the ocular surface, cornea, retina, conjunctiva, meibomian and lacrimal glands, and other ocular structures in the norm and pathology. We are especially interested in experimental papers and review articles that would describe novel findings and hypotheses with regard to the mechanisms of the onset of life-threatening and/or debilitating ocular diseases and pathologies on a molecular level, and, eventually, lead to more effective treatments of those conditions. More often than not, the molecular bases of rare and/or multifactorial diseases are insufficiently studied and poorly understood, which impedes the development of proper treatments and represents a major challenge for health professionals and scientists alike. Obtaining and discussing new information on the molecular mechanisms of these diseases and pathologies, using cell and animal models, as well as human volunteers, would be an important step toward finding cures for those conditions.

Dr. Igor A. Butovich
Guest Editor

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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.

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Published Papers (6 papers)

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Research

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12 pages, 4251 KiB

Open AccessArticle

Fuch’s Endothelial Corneal Dystrophy in Cataract Patients Is Associated with Elevated Levels of Inflammatory Chemokines, but Not Growth Factors, in the Aqueous Humor

by Rafał Fiolka, Edward Wylęgała, Michał Toborek, Dominika Szkodny, Zenon Czuba and Adam Wylęgała

Int. J. Mol. Sci. 2024, 25(3), 1894; https://doi.org/10.3390/ijms25031894 - 4 Feb 2024

Cited by 3 | Viewed by 1556

Abstract

The study investigated a profile of chemokines and growth factors in the aqueous humor (AH) of eyes with Fuch’s endothelial corneal dystrophy (FECD) and cataracts in comparison with cataract patients as a control group. A total of 52 AH samples (26 FECD + cataract and 26 cataract/control) were collected before cataract surgery. None of the patients had any clinically apparent inflammation at the time of AH collection. The AH levels of MCP-1 (CCL2), MIP-1α (CCL3), MIP-1β(CCL4), RANTES (CCL5), eotaxin (CCL11), IP-10 (CXCL10), FGF basic, G-CSF, GM-CSF, PDGF-bb, and VEGF were compared between the groups. The analyses were performed using the Bio-Plex 200 System from Bio-Rad. Among the studied parameters, the AH levels of RANTES, eotaxin, and IP-10 significantly increased in the FECD + cataract eyes, compared with the cataract controls (p < 0.05). Elevated levels of the RANTES, Eotaxin, and IP-10 indicate more intense inflammation in the eyes of patients in the FECD + cataract group. Moreover, these factors exhibit potential as predictive biomarkers for early detection of FECD in cataract patients. The discovery of elevated concentrations of biochemical markers in a patient, who has not yet received a clinical diagnosis, may suggest the need for heightened observation of the other eye to monitor the potential development of FECD. Full article

(This article belongs to the Special Issue Diseases of the Eye and Adnexa: From Cellular and Molecular Mechanisms to Novel Therapeutic Approaches)

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16 pages, 6009 KiB

Open AccessArticle

Dysregulation of Lipid Metabolism in Aging Meibomian Glands and Its Molecular Markers

by Igor A. Butovich, Amber Wilkerson and Seher Yuksel

Int. J. Mol. Sci. 2023, 24(17), 13512; https://doi.org/10.3390/ijms241713512 - 31 Aug 2023

Cited by 1 | Viewed by 1330

Abstract

The main function of exocrine Meibomian glands (MGs) is to produce a lipid-rich secretion called meibum which plays a critical role in maintaining the ocular surface homeostasis of humans and most mammals. The chemical composition of meibum, and its quantity produced by MGs, largely determine whether it can fulfill its role successfully. Aging was frequently associated with the onset of various MG-related pathologies. The goal of this study was to determine how aging affects the chemical composition and quantity of meibum in mice, and identify possible molecular markers of aging. Unbiased, untargeted and targeted lipidomic evaluation of mouse MG lipids was conducted using liquid chromatography—high-resolution mass spectrometry, and the results were analyzed using Principal Component, Orthogonal Projections to Latent Structures Discriminant, and Partial Least Square Discriminant Analyses. We found that aging leads to dysregulation of lipid metabolism in MGs, changing the ratios of major classes of MG lipids (such as wax esters, triacylglycerols, and phospholipids) in a progressive manner. Several lipid species that belong to these groups of MG lipids are proposed as clear markers of aging in a mouse model. Full article

(This article belongs to the Special Issue Diseases of the Eye and Adnexa: From Cellular and Molecular Mechanisms to Novel Therapeutic Approaches)

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20 pages, 9294 KiB

Open AccessArticle

Comparison between Cultivated Oral Mucosa and Ocular Surface Epithelia for COMET Patients Follow-Up

by Eustachio Attico, Giulia Galaverni, Andrea Torello, Elisa Bianchi, Susanna Bonacorsi, Lorena Losi, Rossella Manfredini, Alessandro Lambiase, Paolo Rama and Graziella Pellegrini

Int. J. Mol. Sci. 2023, 24(14), 11522; https://doi.org/10.3390/ijms241411522 - 15 Jul 2023

Cited by 2 | Viewed by 2106

Abstract

Total bilateral Limbal Stem Cell Deficiency is a pathologic condition of the ocular surface due to the loss of corneal stem cells. Cultivated oral mucosa epithelial transplantation (COMET) is the only autologous successful treatment for this pathology in clinical application, although abnormal peripheric corneal vascularization often occurs. Properly characterizing the regenerated ocular surface is needed for a reliable follow-up. So far, the univocal identification of transplanted oral mucosa has been challenging. Previously proposed markers were shown to be co-expressed by different ocular surface epithelia in a homeostatic or perturbated environment. In this study, we compared the transcriptome profile of human oral mucosa, limbal and conjunctival cultured holoclones, identifying Paired Like Homeodomain 2 (PITX2) as a new marker that univocally distinguishes the transplanted oral tissue from the other epithelia. We validated PITX2 at RNA and protein levels to investigate 10-year follow-up corneal samples derived from a COMET-treated aniridic patient. Moreover, we found novel angiogenesis-related factors that were differentially expressed in the three epithelia and instrumental in explaining the neovascularization in COMET-treated patients. These results will support the follow-up analysis of patients transplanted with oral mucosa and provide new tools to understand the regeneration mechanism of transplanted corneas. Full article

(This article belongs to the Special Issue Diseases of the Eye and Adnexa: From Cellular and Molecular Mechanisms to Novel Therapeutic Approaches)

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10 pages, 644 KiB

Open AccessArticle

Functional and Anatomical Outcomes of Anti-Vascular Endothelial Growth Factor Treatment for Exudative Age-Related Macular Degeneration with or without Obstructive Sleep Apnea

by Nan-Ni Chen, Chau-Yin Chen, Jin-Jhe Wang, Heng-Chiao Huang, Wei-Dar Chen, Ching-Lung Chen, Yao-Hsu Yang, Meng-Hung Lin, Ting-Yu Kuo and Chien-Hsiung Lai

Int. J. Mol. Sci. 2023, 24(8), 7285; https://doi.org/10.3390/ijms24087285 - 14 Apr 2023

Cited by 1 | Viewed by 1538

Abstract

(1) To investigate the functional and anatomical outcomes of anti-vascular endothelial growth factor (anti-VEGF) treatment in patients with exudative age-related macular degeneration (AMD) with or without obstructive sleep apnea (OSA); (2) In total, 65 patients with AMD with or without OSA who received three consecutive doses of intravitreal anti-VEGF injections were enrolled. The primary outcomes—best-corrected visual acuity (BCVA) and central macular thickness (CMT)—were assessed at 1 and 3 months. Moreover, morphological changes observed through optical coherence tomography were analyzed; (3) In total, 15 of the 65 patients had OSA and were included in the OSA group; the remaining 50 patients were included in the non-OSA (control) group. At 1 and 3 months after treatment, BCVA and CMT had improved but did not differ significantly between the groups. More patients in the OSA group demonstrated subretinal fluid (SRF) resorption at 3 months after treatment than in the non-OSA group (p = 0.009). Changes in other imaging biomarkers, such as intraretinal cysts, retinal pigment epithelium detachment, hyperreflective dots, and ellipsoid zone disruptions, did not differ significantly between the groups; (4) Our results suggest that the BCVA and CMT outcomes 3 months after anti-VEGF treatment are similar between patients with and without OSA. Moreover, patients with OSA may exhibit superior SRF resorption. A large-scale prospective study is mandatory to evaluate the association between SRF resorption and visual outcomes in AMD patients with OSA. Full article

(This article belongs to the Special Issue Diseases of the Eye and Adnexa: From Cellular and Molecular Mechanisms to Novel Therapeutic Approaches)

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Review

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18 pages, 796 KiB

Open AccessReview

The Variety of Mechanosensitive Ion Channels in Retinal Neurons

by Ji-Jie Pang

Int. J. Mol. Sci. 2024, 25(9), 4877; https://doi.org/10.3390/ijms25094877 - 30 Apr 2024

Cited by 2 | Viewed by 1374

Abstract

Alterations in intraocular and external pressure critically involve the pathogenesis of glaucoma, traumatic retinal injury (TRI), and other retinal disorders, and retinal neurons have been reported to express multiple mechanical-sensitive channels (MSCs) in recent decades. However, the role of MSCs in visual functions and pressure-related retinal conditions has been unclear. This review will focus on the variety and functional significance of the MSCs permeable to K⁺, Na⁺, and Ca²⁺, primarily including the big potassium channel (BK); the two-pore domain potassium channels TRAAK and TREK; Piezo; the epithelial sodium channel (ENaC); and the transient receptor potential channels vanilloid TRPV1, TRPV2, and TRPV4 in retinal photoreceptors, bipolar cells, horizontal cells, amacrine cells, and ganglion cells. Most MSCs do not directly mediate visual signals in vertebrate retinas. On the other hand, some studies have shown that MSCs can open in physiological conditions and regulate the activities of retinal neurons. While these data reasonably predict the crossing of visual and mechanical signals, how retinal light pathways deal with endogenous and exogenous mechanical stimulation is uncertain. Full article

(This article belongs to the Special Issue Diseases of the Eye and Adnexa: From Cellular and Molecular Mechanisms to Novel Therapeutic Approaches)

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22 pages, 2126 KiB

Open AccessReview

Topical Treatment for Retinal Degenerative Pathologies: A Systematic Review

by Lăcrămioara Samoilă, Oliviu Voștinaru, Elena Dinte, Andreea Elena Bodoki, Bogdan-Cezar Iacob, Ede Bodoki and Ovidiu Samoilă

Int. J. Mol. Sci. 2023, 24(9), 8045; https://doi.org/10.3390/ijms24098045 - 28 Apr 2023

Cited by 7 | Viewed by 2963

Abstract

The topical administration of medicines is the preferred route in ocular therapy, at least for the anterior segment of the eye. However, the eye’s inherent functional and biological barriers all work against the active pharmaceutical ingredient (API) to efficiently reach the targeted retinal structures. The main objective of this article is to offer a systematic review of the scientific literature in recent years, focusing on the latest developments of topical treatment intended for retinal degenerative diseases. Database search returned 102 clinical studies, focused on topical treatment for age macular degeneration, macular edemas (in diabetic retinopathy, surgery related or in retinal dystrophies) or glaucoma. After the exclusion of low-powered studies and those combining vitreo-retinal surgery, 35 articles remained for analysis. Currently, the topical treatment of retinal degenerative diseases is limited by the difficulty to deliver effective drug concentrations to the posterior eye structures. However, in the case of drug classes like NSAIDs, the presence of certain molecular and metabolic features for specific representatives makes the topical administration currently feasible in several clinical contexts. For other drug classes, either a fine-tuning of the API’s pharmacokinetic profile or the use of more advanced formulation strategies, such as rationally designed nanostructured drugs and vehicles, crystalline polymorphs or supramolecular complexes, could bring the much awaited breakthrough for a more predictable and controlled delivery towards the retinal structures and could eventually be employed in the future for the development of more effective ways of delivering drugs to the posterior eye, with the ultimate goal of improving their clinical efficacy. Full article

(This article belongs to the Special Issue Diseases of the Eye and Adnexa: From Cellular and Molecular Mechanisms to Novel Therapeutic Approaches)

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