Molecular Mechanisms and Novel Therapeutic Approaches for Eye Diseases

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cell Biology and Pathology".

Deadline for manuscript submissions: 30 September 2024 | Viewed by 6973

Special Issue Editor


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Guest Editor
School of Optometry & Vision Science, University of New South Wales, Sydney, NSW 2052, Australia
Interests: ocular therapeutics; corneal neuropathy; dry eye disease; meibomian gland dysfunction; anterior segment morphology; corneal immunology; ocular surface neurobiology
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Special Issue Information

Dear Colleagues,

This Special Issue, “Molecular Mechanisms and Novel Therapeutic Approaches for Eye Diseases”, will cover a selection of recent research topics, preclinical studies, experimental studies, and current review articles related to the pathomechanisms, etiopathological pathways and management of eye disease, with a special emphasis on ocular surface disease. It will also include papers exploring potential treatment measures to attenuate both anterior and posterior eye disease. Apart from inflammation, understanding several key factors in the pathogenesis of eye diseases (e.g., oxidative stress, neurodegeneration, and neovascularization) open doors to novel therapeutic approaches. The molecular bases of many ophthalmic diseases are often not known, especially for multifactorial diseases. This challenge serves as roadblock in the development of novel therapeutic agents, and represents a major challenge for eye care practitioners. 

Dr. Kofi Asiedu
Guest Editor

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Keywords

  • ocular biomarkers
  • anterior eye therapeutics
  • oxidative stress
  • posterior eye therapeutics
  • corneal immunology
  • ocular inflammation
  • ocular allergies
  • ocular infection
  • neuro-ophthalmic disease.

Published Papers (5 papers)

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Research

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16 pages, 8401 KiB  
Article
Electroretinographical Analysis of the Effect of BGP-15 in Eyedrops for Compensating Global Ischemia–Reperfusion in the Eyes of Sprague Dawley Rats
by Barbara Takács, Anna Szilágyi, Dániel Priksz, Mariann Bombicz, Adrienn Mónika Szabó, Beáta Pelles-Taskó, Ágnes Rusznyák, Ádám Haimhoffer, Rudolf Gesztelyi, Zoltán Szilvássy, Béla Juhász and Balázs Varga
Biomedicines 2024, 12(3), 637; https://doi.org/10.3390/biomedicines12030637 - 13 Mar 2024
Cited by 1 | Viewed by 826
Abstract
Retinal vascular diseases and consequential metabolic disturbances in the eye are major concerns for healthcare systems all around the world. BGP-15, a drug candidate small-molecule [O-(3-piperidino-2-hydroxy-1-propyl) nicotinic amidoxime dihydrochloride], has been formerly demonstrated by our workgroup to be retinoprotective both in the short [...] Read more.
Retinal vascular diseases and consequential metabolic disturbances in the eye are major concerns for healthcare systems all around the world. BGP-15, a drug candidate small-molecule [O-(3-piperidino-2-hydroxy-1-propyl) nicotinic amidoxime dihydrochloride], has been formerly demonstrated by our workgroup to be retinoprotective both in the short and long term. Based on these results, the present study was performed to investigate the efficacy of BGP in an eyedrop formulation containing sulfobutylether-β-cyclodextrin (SBECD), which is a solubility enhancer as well. Electroretinographical evaluations were carried out and BGP was demonstrated to improve both scotopic and photopic retinal a- and b-waves, shorten their implicit times and restore oscillatory potentials after ischemia–reperfusion. It was also observed to counteract retinal thinning after ischemia–reperfusion in the eyes of Sprague Dawley rats. This small-molecule drug candidate is able to compensate for experimental global eye ischemia–reperfusion injury elicited by ligation of blood vessels in rats. We successfully demonstrated that BGP is able to exert its protective effects on the retina even if administered in the form of eyedrops. Full article
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10 pages, 608 KiB  
Article
Dry Eye Para-Inflammation Treatment: Evaluation of a Novel Tear Substitute Containing Hyaluronic Acid and Low-Dose Hydrocortisone
by Davide Borroni, Cosimo Mazzotta, Carlos Rocha-de-Lossada, José-María Sánchez-González, Antonio Ballesteros-Sanchez, María García-Lorente, Francisco Zamorano-Martín, Antonio Spinelli, Domenico Schiano-Lomoriello and Giovanni Roberto Tedesco
Biomedicines 2023, 11(12), 3277; https://doi.org/10.3390/biomedicines11123277 - 11 Dec 2023
Viewed by 1165
Abstract
Purpose: The purpose of this study was to check the efficacy and safety of a novel tear substitute containing hyaluronic acid and low-dose hydrocortisone in the treatment of moderate dry eye disease. Methods: In this prospective randomized study, 38 patients with moderate dry [...] Read more.
Purpose: The purpose of this study was to check the efficacy and safety of a novel tear substitute containing hyaluronic acid and low-dose hydrocortisone in the treatment of moderate dry eye disease. Methods: In this prospective randomized study, 38 patients with moderate dry eye disease were divided into two treatment groups: Group 1 received one drop of 0.2% sodium hyaluronate and 0.001% hydrocortisone four times daily for 3 months, while Group 2 received 0.15% sodium hyaluronate and 3% trehalose at the same dosage. OSDI and SANDE questionnaires, Non-Invasive Break-Up time (NIBUT), Tear Meniscus Height (TMH), meibography, Lipid Layer Thickness (LLT), Tear Break-Up Time (TBUT), Corneal Staining Score (CFS), and Intraocular Pressure (IOP) were evaluated at baseline and after 1, 2, and 3 months of treatment. Results: During the treatment period, Group 1 showed statistically significant improvement in OSDI score (p = 0.002), SANDE score (p = 0.01), NIBUT (p < 0.0001), LLT (p < 0.0001), TBUT (p = 0.01), and CFS (p = 0.02). In Group 2, significant improvement was observed only in the TBUT score (p < 0.05). Comparison of the two groups showed that NIBUT and LLT were significantly different at the end of treatment (p = 0.001 for both comparisons), with more favorable results for sodium hyaluronate and hydrocortisone than for sodium hyaluronate and trehalose. No significant variations in intraocular pressure were observed in either group during the treatment period (p > 0.05). Conclusions: The study confirms that a 3-months treatment with hyaluronic acid 0.2% in combination with low-dose hydrocortisone 0.001% improves the signs and symptoms of moderate DED and that a low-dosage 0.001% hydrocortisone can be helpful in preventing the progression to chronic stages of DED. Full article
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17 pages, 3963 KiB  
Article
TGF-β2 Induces Epithelial–Mesenchymal Transitions in 2D Planer and 3D Spheroids of the Human Corneal Stroma Fibroblasts in Different Manners
by Araya Umetsu, Yosuke Ida, Tatsuya Sato, Masato Furuhashi, Hiroshi Ohguro and Megumi Watanabe
Biomedicines 2023, 11(9), 2513; https://doi.org/10.3390/biomedicines11092513 - 12 Sep 2023
Viewed by 1237
Abstract
To examine the epithelial–mesenchymal transition (EMT) that is induced on the human corneal stroma, two- and three-dimensional (2D and 3D) cultures of human corneal stroma fibroblasts (HCSFs) were used. In this study, HCSF 2D monolayers and 3D spheroids were characterized by (1) scanning [...] Read more.
To examine the epithelial–mesenchymal transition (EMT) that is induced on the human corneal stroma, two- and three-dimensional (2D and 3D) cultures of human corneal stroma fibroblasts (HCSFs) were used. In this study, HCSF 2D monolayers and 3D spheroids were characterized by (1) scanning electron microscopy (SEM), (2) trans-endothelial electrical resistance (TEER) measurements and fluorescein isothiocyanate (FITC)-dextran permeability, (3) cellular metabolic measurements, (4) the physical properties of 3D HCSF spheroids, and (5) the extracellular matrix (ECM) molecule gene expressions, including collagen (COL) 1, 4 and 6, and fibronectin (FN), a tissue inhibitor of metalloproteinase (TIMP) 1–4, matrix metalloproteinase (MMP) 2, 3, 9 and 14, and several endoplasmic reticulum (ER) stress-related factors. In the 2D HCSFs, TGF-β2 concentration-dependently generated (1) a considerable increase in ECM deposits revealed by SEM, (2) an increase in TEER values and a decrease in FITC-dextran permeability, (3) increases in both mitochondrial and glycolytic functions, and a substantial upregulation of COL1, COL4, FN, αSMA, TIMP1, TIMP, and most ER stress-related genes and the downregulation of COL6 and MMP3. In the case of 3D spheroids, TGF-β2 induced the downsizing and stiffening of 3D spheroids and the upregulation of COL6, MMP14, and most ER stress-related genes. These findings suggest that TGF-β2 significantly induced a number of EMT-associated biological events including planar proliferation, cellular metabolic functions, and the production of ECM molecules in the 2D cultured HCSF cells, but these effects were significantly less pronounced in the case of 3D HCSF spheroids. Full article
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11 pages, 751 KiB  
Article
Chronic Kidney Disease Has No Impact on Tear Film Substance P Concentration in Type 2 Diabetes
by Kofi Asiedu, Sultan Alotaibi, Arun V. Krishnan, Natalie Kwai, Ann Poynten, Maria Markoulli and Roshan Dhanapalaratnam
Biomedicines 2023, 11(9), 2368; https://doi.org/10.3390/biomedicines11092368 - 24 Aug 2023
Cited by 1 | Viewed by 1610
Abstract
Purpose: The study aimed to ascertain the potential effects of chronic kidney disease (CKD) on substance P concentration in the tear film of people with type 2 diabetes. Methods: Participants were classified into two groups: type 2 diabetes with concurrent chronic kidney disease [...] Read more.
Purpose: The study aimed to ascertain the potential effects of chronic kidney disease (CKD) on substance P concentration in the tear film of people with type 2 diabetes. Methods: Participants were classified into two groups: type 2 diabetes with concurrent chronic kidney disease (T2DM–CKD (n = 25)) and type 2 diabetes without chronic kidney disease (T2DM–no CKD (n = 25)). Ocular surface discomfort assessment, flush tear collection, in-vivo corneal confocal microscopy, and peripheral neuropathy assessment were conducted. Enzyme-linked immunosorbent assays were utilized to ascertain the levels of tear film substance P in collected flush tears. Correlation analysis, hierarchical multiple linear regression analysis, and t-tests or Mann–Whitney U tests were used in the analysis of data for two-group comparisons. Results: There was no substantial difference between the T2DM–CKD and T2DM–no CKD groups for tear film substance P concentration (4.4 (0.2–50.4) and 5.9 (0.2–47.2) ng/mL, respectively; p = 0.54). No difference was observed in tear film substance P concentration between the low-severity peripheral neuropathy and high-severity peripheral neuropathy groups (4.4 (0.2–50.4) and 3.3 (0.3–40.7) ng/mL, respectively; p = 0.80). Corneal nerve fiber length (9.8 ± 4.6 and 12.4 ± 3.8 mm/mm2, respectively; p = 0.04) and corneal nerve fiber density (14.7 ± 8.5 and 21.1 ± 7.0 no/mm2, respectively; p < 0.01) were reduced significantly in the T2DM–CKD group compared to the T2DM–no CKD group. There were significant differences in corneal nerve fiber density (21.0 ± 8.1 and 15.8 ± 7.7 no/mm2, respectively; p = 0.04) and corneal nerve fiber length (12.9 ± 4.2 and 9.7 ± 3.8 mm/mm2, respectively; p = 0.03) between the low- and high-severity peripheral neuropathy groups. Conclusion: In conclusion, no significant difference in tear film substance P concentration was observed between type 2 diabetes with and without CKD. Corneal nerve loss, however, was more significant in type 2 diabetes with chronic kidney disease compared to type 2 diabetes alone, indicating that corneal nerve morphological measures could serve greater utility as a tool to detect neuropathy and nephropathy-related corneal nerve changes. Full article
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Review

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18 pages, 14777 KiB  
Review
Therapeutic Potential of Antioxidants and Hybrid TEMPOL Derivatives in Ocular Neurodegenerative Diseases: A Glimpse into the Future
by Charles E. Amankwa, Bindu Kodati, Nina Donkor and Suchismita Acharya
Biomedicines 2023, 11(11), 2959; https://doi.org/10.3390/biomedicines11112959 - 1 Nov 2023
Cited by 1 | Viewed by 1259
Abstract
Reactive oxygen species play a significant role in the pathogenesis of various ocular neurodegenerative diseases especially glaucoma, age-related macular degeneration (AMD), and ocular ischemic stroke. Increased oxidative stress and the accumulation of ROS have been implicated in the progression of these diseases. As [...] Read more.
Reactive oxygen species play a significant role in the pathogenesis of various ocular neurodegenerative diseases especially glaucoma, age-related macular degeneration (AMD), and ocular ischemic stroke. Increased oxidative stress and the accumulation of ROS have been implicated in the progression of these diseases. As a result, there has been growing interest in exploring potential therapeutic and prophylactic strategies involving exogenous antioxidants. In recent years, there have been significant advancements in the development of synthetic therapeutic antioxidants for targeting reactive oxygen species (ROS) in neurodegenerative diseases. One area of focus has been the development of hybrid TEMPOL derivatives. In the context of ocular diseases, the application of next-generation hybrid TEMPOL antioxidants may offer new avenues for neuroprotection. By targeting ROS and reducing oxidative stress in the retina and optic nerve, these compounds have the potential to preserve retinal ganglion cells and trabecular meshwork and protect against optic nerve damage, mitigating irreversible blindness associated with these diseases. This review seeks to highlight the potential impact of hybrid TEMPOL antioxidants and their derivatives on ocular neurodegenerative disorders. Full article
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