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Keywords = ocular surface exposure

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21 pages, 1734 KiB  
Review
Oculoplastic Interventions in the Management of Ocular Surface Diseases: A Comprehensive Review
by Seyed Mohsen Rafizadeh, Hassan Asadigandomani, Samin Khannejad, Arman Hasanzade, Kamran Rezaei, Avery Wei Zhou and Mohammad Soleimani
Life 2025, 15(7), 1110; https://doi.org/10.3390/life15071110 - 16 Jul 2025
Viewed by 508
Abstract
This study aimed to comprehensively review surgical interventions for ocular surface diseases (OSDs), including dry eye syndrome (DES), exposure keratopathy, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and ocular graft versus host disease (oGVHD), and to highlight the indications, contraindications, outcomes, and complications [...] Read more.
This study aimed to comprehensively review surgical interventions for ocular surface diseases (OSDs), including dry eye syndrome (DES), exposure keratopathy, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and ocular graft versus host disease (oGVHD), and to highlight the indications, contraindications, outcomes, and complications of various oculoplastic procedures used in their management. A narrative review was performed based on expert-guided selection of relevant studies retrieved from PubMed, Scopus, and Web of Science. Relevant keywords included “ocular surface disease”, “dry eye syndrome”, “exposure keratopathy”, “thyroid eye disease (TED)”, “neurotrophic keratopathy (NK)”, “Stevens-Johnson syndrome”, “toxic epidermal necrolysis”, “punctal occlusion”, “tarsorrhaphy”, “botulinum toxin”, “eyelid loading”, “retractor weakening”, “corneal neurotization (CN)”, “amniotic membrane transplantation (AMT)”, “conjunctival flap”, “ocular graft versus host disease”, and “salivary gland transplantation (SGT)”. Studies addressing surgical approaches for OSDs were included. In conclusion, surgical options for OSDs offer significant benefits when non-invasive treatments fail. Surgical techniques such as punctal occlusion, eyelid fissure narrowing, AMT, and conjunctival flap procedures help stabilize the ocular surface and alleviate symptoms. Advanced methods like CN and SGT target the underlying pathology in refractory cases such as oGVHD. The outcomes vary depending on the disease severity and surgical approach. Each procedure carries specific risks and requires individualized patient selection. Therefore, a tailored approach based on clinical condition, anatomical involvement, and patient factors is essential to achieve optimal results. Ongoing innovations in reconstructive surgery and regenerative medicine are expected to further improve outcomes for patients with OSDs. Full article
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33 pages, 4263 KiB  
Review
Iatrogenic Ocular Surface Complications After Surgery for Ocular and Adnexal Tumors
by Maria Angela Romeo, Andrea Taloni, Massimiliano Borselli, Alessandra Di Maria, Alessandra Mancini, Vincenzo Mollace, Giovanna Carnovale-Scalzo, Vincenzo Scorcia and Giuseppe Giannaccare
Cancers 2025, 17(9), 1384; https://doi.org/10.3390/cancers17091384 - 22 Apr 2025
Viewed by 1264
Abstract
Background/Objectives: The management of ocular tumors often necessitates surgery, either alone or in combination with radiotherapy, chemotherapy, or other modalities. While crucial for tumor control, these treatments can significantly impact the ocular surface, leading to both acute and chronic complications. This review examines [...] Read more.
Background/Objectives: The management of ocular tumors often necessitates surgery, either alone or in combination with radiotherapy, chemotherapy, or other modalities. While crucial for tumor control, these treatments can significantly impact the ocular surface, leading to both acute and chronic complications. This review examines iatrogenic ocular surface diseases resulting from oncologic interventions, emphasizing their pathophysiology, diagnostic challenges, and management strategies. Methods: A literature review was conducted to identify studies on iatrogenic ocular surface complications associated with ocular tumor treatments. Results: Ocular surface complications include direct damage from surgical manipulation, leading to corneal opacities and persistent epithelial defects, as well as dry eye disease secondary to postoperative chemosis. These disruptions may progress to more severe conditions such as keratopathy, corneal ulcers, limbal stem cell deficiency, and stromal scarring, further impairing visual function. Structural alterations contribute to eyelid malpositions—including ectropion, entropion, round eye, and lagophthalmos—which exacerbate exposure-related damage and ocular surface instability. In cases of uveal melanomas, the exposure of episcleral brachytherapy plaques can induce chronic conjunctival irritation, promoting adhesion formation and symblepharon. Surgical interventions disrupt ocular surface homeostasis, while radiotherapy and chemotherapy exacerbate these effects through cytotoxic and inflammatory mechanisms. Conclusions: Preventing and managing iatrogenic ocular surface complications require a multidisciplinary approach involving early diagnosis, personalized treatment strategies, and targeted postoperative care. Comprehensive pre- and postoperative planning is essential to optimize both visual function and long-term ocular surface integrity, ultimately ensuring a balance between oncologic control with functional and aesthetic preservation. Full article
(This article belongs to the Section Cancer Therapy)
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22 pages, 6428 KiB  
Article
Rebamipide Enhances Pathogen Defense and Mitigates Inflammation in a Particulate Matter-Induced Ocular Surface Inflammation Rat Model
by Basanta Bhujel, Se-Heon Oh, Woojune Hur, Seorin Lee, Hun Lee, Ho-Seok Chung and Jae Yong Kim
Int. J. Mol. Sci. 2025, 26(8), 3922; https://doi.org/10.3390/ijms26083922 - 21 Apr 2025
Viewed by 900
Abstract
Particulate matter (PM) exposure is known to induce significant ocular surface inflammation, necessitating effective therapeutic interventions. This study compared the efficacy of 2% rebamipide (REB) with 0.1% hyaluronic acid (HA) eye drops in investigating the anti-inflammatory and pathogen-clearance effects in a PM-induced ocular [...] Read more.
Particulate matter (PM) exposure is known to induce significant ocular surface inflammation, necessitating effective therapeutic interventions. This study compared the efficacy of 2% rebamipide (REB) with 0.1% hyaluronic acid (HA) eye drops in investigating the anti-inflammatory and pathogen-clearance effects in a PM-induced ocular surface inflammation model using Sprague–Dawley (SD) rats. Parameters including clinical signs, histological changes, mucin secretions, inflammatory cytokines, mast cell degranulation, dysregulated cell proliferation, and cellular apoptosis were evaluated. 2% REB alleviated ocular surface inflammation by downregulating the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) inflammatory pathway and upregulating epidermal growth factor receptor (EGFR) signaling, thereby enhancing mucin secretion and promoting pathogen clearance. Histopathological analysis, western blot, and immunohistochemical staining revealed a marked reduction in inflammatory markers including MMP-9, IL-1β, TNF-α, IL-17, and CD-4, decreased mast cell degranulation, increased goblet cell density, and enhanced expression of mucins, including MUC5AC and MUC16, in the 2% REB-treated group compared to the 0.1% HA-treated and PM-exposed groups. Moreover, 2% REB demonstrated decreased apoptosis (TUNEL) and reduced uncontrolled cell proliferation (Ki67), indicating improved cellular integrity. In conclusion, 2% REB is a promising treatment option for PM-induced ocular surface inflammation in a rat model compared with 0.1% HA, offering the benefits of reducing inflammation, clearing pathogens, and protecting overall ocular health. Full article
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11 pages, 2896 KiB  
Article
Hydrophobic Silicon Quantum Dots for Potential Imaging of Tear Film Lipid Layer
by Sidra Sarwat, Fiona Stapleton, Mark D. P. Willcox, Peter B. O’Mara and Maitreyee Roy
Nanomaterials 2025, 15(7), 552; https://doi.org/10.3390/nano15070552 - 4 Apr 2025
Viewed by 1340
Abstract
The tear film, consisting of the aqueous and lipid layers, maintains the homeostasis of the ocular surface; therefore, when disturbed, it can cause dry eye, which affects millions of people worldwide. Understanding the dynamics of the tear film layers is essential for developing [...] Read more.
The tear film, consisting of the aqueous and lipid layers, maintains the homeostasis of the ocular surface; therefore, when disturbed, it can cause dry eye, which affects millions of people worldwide. Understanding the dynamics of the tear film layers is essential for developing efficient drug delivery systems for dry eye disease. Quantum dots (QDs) offer the potential for real-time monitoring of tear film and evaluating its dynamics. Hydrophilic silicon QDs (Si-QDs) have already been optimised to image the aqueous layer of the tear film. This study was conducted to optimise hydrophobic Si-QDs to image the lipid layer of the tear film. Si-QDs were synthesised in solution and characterised by transmission electron microscope and spectrofluorophotometry. The fluorescence emission of Si-QDs was monitored in vitro when mixed with artificial tears. The cytotoxicity was assessed in cultured human corneal epithelial cells using an MTT assay following 24 h of exposure. Si-QDs were 2.65 ± 0.35 nm in size and were non-toxic at <16 µg/mL. Si-QDs emitted stable green fluorescence for 20 min but demonstrated aggregation at higher concentrations. These findings highlight the potential of hydrophobic Si-QDs as a biomarker for the real-time imaging of the tear film lipid layer. However, further research on surface functionalisation and preclinical evaluations are recommended for enhanced solubility and biocompatibility in the ocular surface. Full article
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14 pages, 3890 KiB  
Article
Potential Role of Malassezia restricta in Pterygium Development
by Martina Paradzik Simunovic, Marina Degoricija, Jelena Korac-Prlic, Mladen Lesin, Robert Stanic, Livia Puljak, Ivana Olujic, Josipa Marin Lovric, Ana Vucinovic, Zana Ljubic, James Thissen, Car Reen Kok, Crystal Jaing, Kajo Bucan and Janos Terzic
Int. J. Mol. Sci. 2025, 26(7), 2976; https://doi.org/10.3390/ijms26072976 - 25 Mar 2025
Cited by 1 | Viewed by 620
Abstract
Pterygium is a condition affecting the ocular surface, marked by a triangular-shaped growth of fibrotic tissue extending from the nasal conjunctiva toward the corneal center, potentially causing visual impairment. While ultraviolet (UV )light exposure is the primary risk factor for pterygium, its underlying [...] Read more.
Pterygium is a condition affecting the ocular surface, marked by a triangular-shaped growth of fibrotic tissue extending from the nasal conjunctiva toward the corneal center, potentially causing visual impairment. While ultraviolet (UV )light exposure is the primary risk factor for pterygium, its underlying cause remains unclear. In order to better understand the true genesis of pterygium development, we investigated pterygium tissue and compared it with healthy conjunctiva controls. Given the eye’s direct environmental exposure, we analyzed the microbiota composition using metagenomic sequencing of pterygium tissue to identify microbes potentially associated with this condition. Metagenomic sequencing revealed a higher prevalence of the fungus Malassezia restricta in five pterygium samples, confirmed by in situ hybridization. The CHIT1 gene, which plays a role in antifungal defenses, displayed the highest expression in five pterygium tissue samples compared to healthy conjunctiva controls, suggesting the potential involvement of Malassezia restricta in pterygium development. Gene expression profiling of pterygium highlighted an IL-33 and IL-4 gene expression signature, along with an increased presence of M2 macrophages, emphasizing their role in promoting fibrosis—a hallmark feature of pterygium. The detection of Malassezia restricta in the pterygium samples and associated molecular changes provides novel insights into the ocular microbiome and raises the possibility of Malassezia’s involvement in pterygium pathology. Full article
(This article belongs to the Section Molecular Microbiology)
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16 pages, 473 KiB  
Systematic Review
Visual Functioning and Mental Health in the Digital Age
by Vanja Kopilaš, Dora Korać, Lovorka Brajković and Mirko Kopilaš
J. Clin. Med. 2025, 14(5), 1557; https://doi.org/10.3390/jcm14051557 - 26 Feb 2025
Viewed by 1479
Abstract
Background/Objectives: Considering the omnipresence of digital devices in every aspect of our lives, and from an increasingly younger age, digital eye strain (DES) and dry eye disease (DED) have become a global concern. The main objective of this paper is to conduct [...] Read more.
Background/Objectives: Considering the omnipresence of digital devices in every aspect of our lives, and from an increasingly younger age, digital eye strain (DES) and dry eye disease (DED) have become a global concern. The main objective of this paper is to conduct a systematic review of the literature on the relationship between digital screen use and ocular surface health, as well as the potential negative impact of impaired visual functioning on certain aspects of mental health and daily performance. Methods: Using the PRISMA method, the screening and study selection process resulted in the inclusion of 15 papers published in the electronic databases PubMed and WoS. Results: The findings highlight the prolonged use of digital devices and the concerning prevalence of DED or DES symptoms across different populations. A significant relationship was found between DED and DES symptoms and mental health outcomes, including depression, anxiety, and stress. Furthermore, higher frequency and severity of DED or DES symptoms was associated with reduced sleep quality and difficulties in certain aspects of daily functioning. Conclusions: Given the ongoing exposure to digital devices and increasing prevalence of DED and DES symptoms across all age groups, there is a need to design interventions and programs focused on preserving ocular surface health and improving subjective well-being. The multifaceted impact these symptoms have on physical and mental health, as well as daily functioning, requires a holistic approach, integrating ergonomic interventions, digital hygiene, and mental health support. Full article
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16 pages, 8767 KiB  
Article
Senescence and Stress Signaling Pathways in Corneal Cells After Nitrogen Mustard Injury
by Khandaker N. Anwar, Mohammad Soleimani, Mohammad Javad Ashraf, Amirhossein Moghtader, Raghuram Koganti, Seyyedehfatemeh Ghalibafan, Mahbod Baharnoori, Zohreh Arabpour, Kasra Cheraqpour, Aron M. Sebhat, Mansour Abtahi, Xincheng Yao, Mahmood Ghassemi and Ali R. Djalilian
Cells 2024, 13(23), 2021; https://doi.org/10.3390/cells13232021 - 6 Dec 2024
Cited by 2 | Viewed by 1194
Abstract
Mustard gas keratopathy (MGK), a complication of exposure to sulfur mustard, is a blinding ocular surface disease involving key cellular pathways, including apoptosis, oxidative stress, and inflammation. Recent studies indicate that cellular senescence contributes to the pathophysiology of mustard gas toxicity. This study [...] Read more.
Mustard gas keratopathy (MGK), a complication of exposure to sulfur mustard, is a blinding ocular surface disease involving key cellular pathways, including apoptosis, oxidative stress, and inflammation. Recent studies indicate that cellular senescence contributes to the pathophysiology of mustard gas toxicity. This study aimed to assess senescence and stress-related pathways—particularly mitogen-activated protein kinase (MAPK) signaling—in nitrogen mustard (NM)-induced corneal injury. In vitro, primary human corneal epithelial (P-HCECs), primary human corneal mesenchymal stromal cells (hcMSCs), and human corneal–limbal epithelial cell (HCLE) lines were exposed to varying concentrations of NM. The results demonstrated a dose-dependent increase in cellular senescence, characterized by reduced Ki67 expression, elevated p16, and p21 mRNA levels, as well as activation of the MAPK pathway activation. Treatment with a selective p38-MAPK inhibitor significantly reduced senescence markers and improved cell proliferation following exposure to NM. Overall, these studies indicate that NM exposure triggers cellular senescence and stress-related MAPK signaling, while p38-MAPK inhibition mitigates these effects, suggesting a potential therapeutic strategy. Full article
(This article belongs to the Special Issue Mechanism of Cell Signaling during Eye Development and Diseases)
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12 pages, 243 KiB  
Review
Digital Applications for Videoterminal-Associated Dry Eye Disease
by Maria Angela Romeo, Giulia Coco, Andrea Taloni, Giovanna Carnovale-Scalzo, Vincenzo Scorcia and Giuseppe Giannaccare
Vision 2024, 8(4), 67; https://doi.org/10.3390/vision8040067 - 28 Nov 2024
Cited by 1 | Viewed by 2274
Abstract
Dry eye disease (DED) has become increasingly prevalent in the digital era, largely due to prolonged screen exposure. The excessive use of digital devices contributes to inappropriate blink frequency and dynamics, leading to ocular surface dryness and discomfort. Additionally, digital screen use has [...] Read more.
Dry eye disease (DED) has become increasingly prevalent in the digital era, largely due to prolonged screen exposure. The excessive use of digital devices contributes to inappropriate blink frequency and dynamics, leading to ocular surface dryness and discomfort. Additionally, digital screen use has broader implications for systemic health, including visual strain, headaches, and disrupted circadian rhythms caused by blue light exposure. Previous studies have shown that prolonged screen time correlates with altered blink frequency and increased symptom severity in DED patients, exacerbating the imbalance in tear film production and evaporation. Blinking dynamics, particularly blink rate and completeness, are crucial in maintaining ocular surface moisture. Incomplete blinking impairs meibomian gland function, reducing lipid secretion, which is essential for preventing tear evaporation. Raising patient awareness through educational material, ergonomic adjustments, and blinking exercises has been shown to mitigate these effects. Digital tools that provide targeted educational interventions can be particularly effective in improving blink dynamics and overall ocular comfort. This study evaluates the efficacy of digital applications in optimizing blinking dynamics and enhancing tear film stability. The findings suggest that these innovations improve patient outcomes by encouraging healthier eye care practices. However, further research is needed to assess their long-term impact across diverse populations. Full article
13 pages, 2424 KiB  
Article
Comparison of Biomarkers Playing a Role in Pterygium Development in Pterygium and Recurrent Pterygium Tissues
by Özgür Eroğul and Serkan Şen
Diagnostics 2024, 14(23), 2619; https://doi.org/10.3390/diagnostics14232619 - 21 Nov 2024
Cited by 1 | Viewed by 1264
Abstract
Background/Objectives: Pterygium is a nonneoplastic elastotic degeneration characterized by subepithelial growth. It manifests as an ocular lesion originating from the bulbar conjunctiva, extending to the corneal surface, and reaching the visual axis in some cases. Although the exact cause is unknown, prolonged exposure [...] Read more.
Background/Objectives: Pterygium is a nonneoplastic elastotic degeneration characterized by subepithelial growth. It manifests as an ocular lesion originating from the bulbar conjunctiva, extending to the corneal surface, and reaching the visual axis in some cases. Although the exact cause is unknown, prolonged exposure to ultraviolet radiation is considered the most significant contributing factor. Chronic irritation and actinic damage are likely responsible for the typical fibrovascular reactions observed in pterygium. Additionally, growth factors, cytokines, and matrix metalloproteinases play roles in the pathogenesis of pterygium. This study compared recurrent and primary pterygium cases at the molecular level to gain new insights into the etiology of pterygium. Methods: Total protein was extracted from surgical samples of patients with primary and recurrent pterygium, and the levels of transforming growth factor beta 1 (TGF-β1), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), IL-8, and IL-10 were analyzed using the enzyme-linked immunosorbent assay technique. Target gene expression levels were analyzed using the ΔΔCt method after cDNA synthesis from isolated RNA, with normalization to GAPDH and quantification performed with SYBR Green PCR Master Mix. Results: Among the studied cytokines, IL-10 levels were higher in primary pterygium than in recurrent pterygium (722.0 ± 600.9/421.4 ± 266.8) (p = 0.0054). Other cytokines (IL-6, IL-8, IL-1β, and TGF-β1) were detected at similar levels in both primary and recurrent pterygium (p = 0.2986). Additionally, the TGF-β1 gene expression was found to be significantly upregulated in recurrent pterygium tissue compared to primary pterygium tissue (p = 0.034). Conclusions: This increase suggests that TGF-β1 may contribute to the recurrence mechanisms of pterygium through processes such as fibroblast activation and tissue remodeling. The higher levels of IL-10 in primary pterygium compared to recurrent pterygium indicate an enhanced early protective response aimed at limiting pterygium progression and controlling the inflammatory process. Full article
(This article belongs to the Special Issue Eye Diseases: Diagnosis and Management—2nd Edition)
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21 pages, 1858 KiB  
Review
Pathological Mechanisms of Particulate Matter-Mediated Ocular Disorders: A Review
by Jung-Hwa Han, Chaima Amri, Hyesook Lee and Jin Hur
Int. J. Mol. Sci. 2024, 25(22), 12107; https://doi.org/10.3390/ijms252212107 - 11 Nov 2024
Cited by 6 | Viewed by 2263
Abstract
Air pollution presents a severe risk to public health, with particulate matter (PM) identified as a significant hazardous element. However, despite the eye organ being constantly exposed to air pollution, only recently has the impact of PM on ocular health caught the attention [...] Read more.
Air pollution presents a severe risk to public health, with particulate matter (PM) identified as a significant hazardous element. However, despite the eye organ being constantly exposed to air pollution, only recently has the impact of PM on ocular health caught the attention of researchers and healthcare professionals. By compiling pertinent data, this paper aims to enhance our understanding of the underlying pathological mechanisms of PM-mediated ocular disorders and facilitate the development of effective treatment strategies. Recent data support the association between exposure to PM and the development of ocular pathologies such as dry eye syndrome, retinal atherosclerosis, and glaucoma. Based on the results of multiple studies, PM exposure can lead to oxidative stress, inflammation, autophagy, cell death, and, ultimately, the development of ophthalmic diseases. This review aims to consolidate the latest findings on PM-mediated ocular diseases by summarizing the outcomes from epidemiological, in vitro, and in vivo studies on ocular surface and retinal disorders as well as other relevant ophthalmic disorders. Full article
(This article belongs to the Special Issue Environmentally Induced Oxidative Stress Toxicology)
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16 pages, 6809 KiB  
Article
A New Approach to Evaluate the Bactericidal Activity of Different Antiseptic Ophthalmic Preparations Used as Surgical Prophylaxis
by Sara Caldrer, Niccolò Deotto, Marco G. Prato, Natasha Gianesini, Milena Bernardi, Pierantonio Orza, Federico G. Gobbi, Grazia Pertile and Chiara Piubelli
Antibiotics 2024, 13(11), 1051; https://doi.org/10.3390/antibiotics13111051 - 6 Nov 2024
Viewed by 1378
Abstract
Background: A survey conducted by the European Observatory on Cataract Surgery showed high heterogeneity in the use of antiseptics both preoperatively and in the operating room, highlighting the absence of a global consensus regarding ocular infection prophylaxis in cataract surgery. Methods: [...] Read more.
Background: A survey conducted by the European Observatory on Cataract Surgery showed high heterogeneity in the use of antiseptics both preoperatively and in the operating room, highlighting the absence of a global consensus regarding ocular infection prophylaxis in cataract surgery. Methods: The antibacterial activity of seven antiseptic ophthalmic formulations (AOFs) registered as medical devices and the two most common disinfectants were evaluated in vitro against five bacterial species. The viability of bacterial strains after exposure to the antiseptic was evaluated with different techniques: the in vitro Minimum Inhibitory Concentration and the subsequent Minimum Bactericidal Concentration, performed on liquid and solid culture medium. Furthermore, a real-time assessment of bacterial viability was conducted using double staining for live/dead bacterial cells by fluorimetric assay. This evaluation was performed on both the time-killing curve and the tear dilution effect test. Results: We observed a high variability across the different AOFs in terms of inhibitory/bactericidal concentration and timing on Gram-positive and Gram-negative bacterial classes. The results indicated that among the tested AOFs, Visuprime, Iodim, and Oftasteril were the most rapid and effective for ocular surface disinfection against the tested bacterial species. Conclusions: The obtained results can support the clinician’s choice of the most suitable AOF for the prevention and treatment of ophthalmic infections associated with surgery. Full article
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13 pages, 4286 KiB  
Article
A Selective Melatonin 2 Receptor Agonist, IIK7, Relieves Blue Light-Induced Corneal Damage by Modulating the Process of Autophagy and Apoptosis
by Hyeon-Jeong Yoon, Enying Jiang, Jingting Liu, Hui Jin, Hee Su Yoon, Ji Suk Choi, Ja Young Moon and Kyung Chul Yoon
Int. J. Mol. Sci. 2024, 25(20), 11243; https://doi.org/10.3390/ijms252011243 - 19 Oct 2024
Cited by 2 | Viewed by 3528
Abstract
This study aims to investigate the effect of the selective MT2 receptor agonist, IIK7, on corneal autophagy and apoptosis, aiming to reduce corneal epithelial damage and inflammation from blue light exposure in mice. Eight-week-old C57BL/6 mice were divided into BL-exposed (BL) and BL-exposed [...] Read more.
This study aims to investigate the effect of the selective MT2 receptor agonist, IIK7, on corneal autophagy and apoptosis, aiming to reduce corneal epithelial damage and inflammation from blue light exposure in mice. Eight-week-old C57BL/6 mice were divided into BL-exposed (BL) and BL-exposed with IIK7 treatment (BL + IIK7 group). Mice underwent blue light exposure (410 nm, 100 J) twice daily with assessments at baseline and on days 3, 7, and 14. Corneal samples were analyzed for MT2 receptor expression, autophagy markers (LC3-II and p62), and apoptosis indicators (BAX expression and TUNEL assay). Then, mice were assigned to normal control, BL, and BL + IIK7. Ocular surface parameters, including corneal fluorescein staining scores, tear volume, and tear film break-up time, were evaluated on days 7 and 14. On day 14, reactive oxygen species (ROS) levels and CD4+ IFN-γ+ T cells percentages were measured. The BL group exhibited higher LC3-II and p62 expression, while the BL + IIK7 group showed reduced expression (p < 0.05). The TUNEL assay showed reduced apoptosis in the BL + IIK7 group compared to the BL group. ROS levels were lower in the BL + IIK7 group. The BL + IIK7 group showed improved ocular surface parameters, including decreased corneal fluorescein staining and increased tear volume. The percentages of CD4+ IFN-γ+ T cells indicated reduced inflammatory responses in the BL + IIK7 group. The MT2 receptor agonist IIK7 regulates corneal autophagy and apoptosis, reducing corneal epithelial damage and inflammation from blue light exposure. Full article
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10 pages, 3169 KiB  
Article
Experimental Study on Ocular Surface Protection by Soft Contact Lenses Due to Volcanic Ash Exposure
by Hiroshi Toshida, Yusuke Matsuzaki and Masahiro Miyazaki
J. Clin. Med. 2024, 13(17), 5281; https://doi.org/10.3390/jcm13175281 - 6 Sep 2024
Viewed by 1181
Abstract
Background: Sudden volcanic eruptions can lead to volcanic ash entering the eyes, causing severe discomfort and complicating evacuation efforts. The specific effects of volcanic ash on ocular tissues, especially when wearing soft contact lenses (SCLs), are not well documented, prompting this experimental [...] Read more.
Background: Sudden volcanic eruptions can lead to volcanic ash entering the eyes, causing severe discomfort and complicating evacuation efforts. The specific effects of volcanic ash on ocular tissues, especially when wearing soft contact lenses (SCLs), are not well documented, prompting this experimental investigation. Methods: White rabbits with normal eyes were randomly divided into three groups: (1) a bare eye group: bare eye + volcanic ash exposure + eye washing, (2) an SCL group: SCL-wearing eye + volcanic ash exposure + eye washing, and (3) a control group: eye washing only. In groups 1 and 2, volcanic ash was applied to one eye under topical anesthesia, followed by immediate saline rinsing. Slit-lamp microscopy and histopathological analysis were conducted after euthanasia. Results: Slit-lamp and histopathological examinations revealed more significant corneal and conjunctival erosion in the bare eye group compared to the SCL group, which showed limited damage. The control group displayed no ocular damage. Conclusions: Guidelines from the “Volcanic Ash Health Effects: A Guide for the Public” by the National Research Institute for Earth Science and Disaster Resilience recommend removing SCLs during ashfall. Our findings suggest that the damage to the corneal and conjunctival epithelium is less severe in SCL-wearing eyes than in bare eyes, recommending that SCL wearers prioritize evacuation over lens removal during sudden ashfall. Full article
(This article belongs to the Special Issue Clinical Advances and Management in Corneal Diseases)
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16 pages, 3434 KiB  
Review
Cellular Stress in Dry Eye Disease—Key Hub of the Vicious Circle
by Gysbert-Botho van Setten
Biology 2024, 13(9), 669; https://doi.org/10.3390/biology13090669 - 28 Aug 2024
Cited by 1 | Viewed by 2240
Abstract
Disturbance or insufficiency of the tear film challenges the regulatory systems of the ocular surfaces. The reaction of the surfaces includes temporary mechanisms engaged in the preservation of homeostasis. However, strong or persisting challenges can lead to the potential exhaustion of the coping [...] Read more.
Disturbance or insufficiency of the tear film challenges the regulatory systems of the ocular surfaces. The reaction of the surfaces includes temporary mechanisms engaged in the preservation of homeostasis. However, strong or persisting challenges can lead to the potential exhaustion of the coping capacity. This again activates the vicious circle with chronic inflammation and autocatalytic deterioration. Hence, the factors challenging the homeostasis should be addressed in time. Amongst them are a varying osmolarity, constant presence of small lesions at the epithelium, acidification, attrition with mechanical irritation, and onset of pain and discomfort. Each of them and, especially when occurring simultaneously, impose stress on the coping mechanisms and lead to a stress response. Many stressors can culminate, leading to an exhaustion of the coping capacity, outrunning normal resilience. Reaching the limits of stress tolerance leads to the manifestation of a lubrication deficiency as the disease we refer to as dry eye disease (DED). To postpone its manifestation, the avoidance or amelioration of stress factors is one key option. In DED, this is the target of lubrication therapy, substituting the missing tear film or its components. The latter options include the management of secondary sequelae such as the inflammation and activation of reparative cascades. Preventive measures include the enhancement in resilience, recovery velocity, and recovery potential. The capacity to handle the external load factors is the key issue. The aim is to guard homeostasis and to prevent intercellular stress responses from being launched, triggering and invigorating the vicious circle. Considering the dilemma of the surface to have to cope with increased time of exposure to stress, with simultaneously decreasing time for cellular recovery, it illustrates the importance of the vicious circle as a hub for ocular surface stress. The resulting imbalance triggers a continuous deterioration of the ocular surface condition. After an initial phase of the reaction and adaption of the ocular surface to the surrounding challenges, the normal coping capacity will be exhausted. This is the time when the integrated stress response (ISR), a protector for cellular survival, will inevitably be activated, and cellular changes such as altered translation and ribosome pausing are initiated. Once activated, this will slow down any recovery, in a phase where apoptosis is imminent. Premature senescence of cells may also occur. The process of prematurization due to permanent stress exposures contributes to the risk for constant deterioration. The illustrated flow of events in the development of DED outlines that the ability to cope, and to recover, has limited resources in the cells at the ocular surface. The reduction in and amelioration of stress hence should be one of the key targets of therapy and begin early. Here, lubrication optimization as well as causal treatment such as the correction of anatomical anomalies (leading to anatomical dry eye) should be a prime intent of any therapy. The features of cellular stress as a key hub for the vicious circle will be outlined and discussed. Full article
(This article belongs to the Special Issue New Horizons in Ocular Surface Biology)
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24 pages, 5452 KiB  
Article
Formulation of Polymeric Nanoparticles Loading Baricitinib as a Topical Approach in Ocular Application
by Negar Beirampour, Paola Bustos-Salgado, Núria Garrós, Roya Mohammadi-Meyabadi, Òscar Domènech, Joaquim Suñer-Carbó, María José Rodríguez-Lagunas, Garyfallia Kapravelou, María Jesús Montes, Ana Calpena and Mireia Mallandrich
Pharmaceutics 2024, 16(8), 1092; https://doi.org/10.3390/pharmaceutics16081092 - 20 Aug 2024
Cited by 4 | Viewed by 1786
Abstract
Topical ocular drug delivery faces several challenges due to the eye’s unique anatomy and physiology. Physiological barriers, tear turnover, and blinking hinder the penetration of drugs through the ocular mucosa. In this context, nanoparticles offer several advantages over traditional eye drops. Notably, they [...] Read more.
Topical ocular drug delivery faces several challenges due to the eye’s unique anatomy and physiology. Physiological barriers, tear turnover, and blinking hinder the penetration of drugs through the ocular mucosa. In this context, nanoparticles offer several advantages over traditional eye drops. Notably, they can improve drug solubility and bioavailability, allow for controlled and sustained drug release, and can be designed to specifically target ocular tissues, thus minimizing systemic exposure. This study successfully designed and optimized PLGA and PCL nanoparticles for delivering baricitinib (BTB) to the eye using a factorial design, specifically a three-factor at five-levels central rotatable composite 23+ star design. The nanoparticles were small in size so that they would not cause discomfort when applied to the eye. They exhibited low polydispersity, had a negative surface charge, and showed high entrapment efficiency in most of the optimized formulations. The Challenge Test assessed the microbiological safety of the nanoparticle formulations. An ex vivo permeation study through porcine cornea demonstrated that the nanoparticles enhanced the permeability coefficient of the drug more than 15-fold compared to a plain solution, resulting in drug retention in the tissue and providing a depot effect. Finally, the in vitro ocular tolerance studies showed no signs of irritancy, which was further confirmed by HET-CAM testing. Full article
(This article belongs to the Topic New Challenges in the Cosmetics Industry)
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