Search Results (127)

Cataracts remain the leading cause of blindness worldwide, and surgery is currently the only effective clinical treatment, as no pharmacological therapy has yet been validated. Here, we explore Fullerenol, a hydroxylated fullerene derivative formulated as eye drops, as a potential nanomedicine for delaying cataract onset and progression. In UVB-induced mouse cataract models, topical Fullerenol preserved the lens transparency and histological structure. In human lens epithelial cells, Fullerenol reduced the oxidative stress, restored the mitochondrial function, alleviated the DNA damage, and suppressed the cellular senescence. RNA sequencing and pathway enrichment analyses further indicated that Fullerenol modulated the oxidative stress- and senescence-associated signaling pathways, including MAPK and TGF-β cascades, while downregulating the p53–CDKN1A (p21) axis. These findings provide new evidence that Fullerenol can mitigate photo-oxidative damage and age-related cellular dysfunction, highlighting its promise as a non-invasive and clinically translatable nanomedicine strategy for cataract management. Full article

Diabetic cataract (DC) is a major complication of diabetes, with human lens epithelial cells (HLECs) playing a central role in its pathogenesis. Gigantol, a natural compound, has demonstrated protective effects against HLEC damage, yet its underlying mechanisms, particularly concerning cellular biophysical properties, remain poorly understood. This study investigated the protective role of gigantol against high-glucose-induced damage in HLECs, with a specific focus on alterations in cellular biophysical properties. Using a multi-technique approach including transmission electron microscopy (TEM), atomic force microscopy, laser scanning confocal microscopy, and Raman spectroscopy, we analyzed changes in ultrastructure, morphology, stiffness, roughness, membrane fluidity, and cytoskeletal organization. Treatment with gigantol effectively restored cellular ultrastructure, mitigated cytoskeletal disruption, and normalized key biomechanical properties: it reduced cell stiffness and roughness by approximately one-fourth, increased cell height by nearly onefold, and enhanced membrane fluidity by one-fifth. Raman spectroscopy indicated that gigantol improved membrane fluidity by modulating lipid bilayer structure, specifically through alterations in –CH₂– bending and –C=C– stretching modes. These findings demonstrate that gigantol protects HLECs from high-glucose-induced damage not only by biochemical means but also by restoring cellular biophysical homeostasis. This study provides novel biophysical–pathological insights into the anti-cataract mechanism of gigantol, highlighting its potential as a therapeutic agent that targets both biochemical and biophysical aspects of DC. Full article

The controlled pro-inflammatory immune response is critical for fighting against external and endogenous threats, such as microbes/pathogens, allergens, xenobiotics, various antigens, and dying host cells and their mediators (DNA, RNA, and nuclear proteins) released into the circulation and cytosol (PAMPs, MAMPs, and DAMPs). Several pattern recognition receptors (PRRs) and their downstream adaptor molecules, expressed by innate and adaptive immune cells, are critical in generating the inflammatory immune response by recognizing PAMPs, MAMPs, and DAMPs. However, their dysregulation may predispose the host to develop inflammation-associated organ damage, neurodegeneration, autoimmunity, cancer, and even death due to the absence of the inflammation resolution phase. The cytosolic calcium (Ca²⁺) level regulates the survival, proliferation, and immunological functions of immune cells. Cysteine-rich proteases, specifically calpains, are Ca²⁺-dependent proteases that become activated during inflammatory conditions, playing a critical role in the inflammatory process and associated organ damage. Therefore, this article discusses the expression and function of calpain-1 and calpain-2 (ubiquitous calpains) in various innate (epithelial, endothelial, dendritic, mast, and NK cells, as well as macrophages) and adaptive (T and B cells) immune cells, affecting inflammation and immune regulation. As inflammatory diseases are on the rise due to several factors, such as environment, lifestyle, and an aging population, we must not just investigate but strive for a deeper understanding of the inflammation and immunoregulation under the calpain system (calpain-1 and calpain-2 and their endogenous negative regulator calpastatin) lens, which is ubiquitous and senses cytosolic Ca²⁺ changes to impact immune response. Full article

Corneal nerves play a crucial role in maintaining ocular surface homeostasis by supporting the functional integrity of corneal epithelial, stromal, and endothelial cells; modulating tear secretion; and facilitating sensory responses essential for overall ocular health. With advancing age, these highly specialized peripheral sensory fibers undergo progressive attrition and morphologic distortion driven by the canonical hallmarks of aging including genomic instability, impaired proteostasis, mitochondrial dysfunction, and chronic low-grade inflammation. The resulting neuro-immune dysregulation reduces trophic support, delays wound healing, and predisposes older adults to dry-eye disease, neurotrophic keratopathy, and postsurgical hypoesthesia. Age-exacerbating cofactors including diabetes, dyslipidemia, neurodegenerative disorders, topical preservatives, chronic contact-lens wear, herpes zoster ophthalmicus, and ocular-surface hypoxia further accelerate sub-basal nerve rarefaction and functional decline. This review provides an overview of age-related physiological alterations in ocular surface nerves, with a particular emphasis on corneal innervation. It also discusses risk factors that speed up these changes. Given the inherently limited regenerative capacity of corneal nerves and their inability to fully restore to baseline conditions following injury or degeneration, it is critical to identify and develop effective strategies aimed at mitigating or delaying physiological nerve degeneration and promoting nerve regeneration. This review also brings up emerging therapeutic strategies, including regenerative medicine, neuroprotective agents, and lifestyle interventions aimed at mitigating age-related corneal nerve degeneration. Full article

Ophthalmic lens coatings are increasingly designed to combine optical, mechanical, and biological functions. This systematic review, registered in PROSPERO and conducted according to PRISMA 2020 guidelines, synthesized 54 experimental, preclinical, and clinical studies on coatings for spectacle lenses, contact lenses, and intraocular lenses. Spectacle lens studies consistently showed that anti-reflective and blue-light filtering coatings reduce glare perception, improve contrast sensitivity, and provide UV protection, while laboratory tests demonstrated significant reductions in impact resistance, with fracture energy of CR-39 lenses decreasing by up to 63% when coated. Contact lens research revealed that plasma and polymeric coatings reduce water contact angles from >100° to <20°, enhancing wettability, while antimicrobial strategies such as melamine binding or nanoparticle-based films achieved >80% reductions in bacterial adhesion. Drug-eluting approaches sustained antibiotic or antioxidant release for periods ranging from 24 h to 6 days, with improved ocular bioavailability compared with drops. Intraocular lens studies demonstrated that heparin surface modifications reduced postoperative flare and anterior chamber cells, and phosphorylcholine or alkylphosphocholine coatings suppressed lens epithelial cell proliferation. Drug-loaded coatings with methotrexate, gefitinib, or amikacin significantly inhibited posterior capsule opacification and infection in ex vivo and animal models. Collectively, coatings improve visual comfort, photoprotection, wettability, and biocompatibility, but clinical translation requires solutions to mechanical trade-offs, long-term stability, and regulatory challenges. Full article

Background: This study aimed to evaluate the influence of scleral contact lens (SCL) wear on optical coherence tomography (OCT) scan quality and structural measurements in patients with keratoconus. Methods: This retrospective observational study included 28 eyes of 28 keratoconus patients. All participants underwent a comprehensive ophthalmologic evaluation, including corneal topography and spectral-domain OCT (Optopol REVO 60). Two OCT measurement sessions were performed on the same day: one without SCLs and one after a 30–75 min adaptation period with Mini Misa^® scleral lenses. Recorded parameters included corneal and epithelial thicknesses, ganglion cell–inner plexiform layer (GCIPL) thickness, retinal nerve fiber layer (RNFL) thickness, and device-reported quality index (QI). Correlation analyses between topographic values, age, and OCT parameters were also conducted. Results: The mean age of participants was 32.96 ± 13.72 years. SCL wear significantly decreased anterior segment QI (6.76 ± 1.73 vs. 5.57 ± 2.34, p = 0.019) but improved posterior segment QI in both the ganglion (2.52 ± 1.03 vs. 5.76 ± 2.17, p < 0.001) and disc (2.82 ± 0.94 vs. 4.39 ± 1.87, p < 0.001) modules. Central corneal thickness remained stable, while central epithelial thickness decreased slightly (50.53 ± 6.66 µm vs. 47.59 ± 7.20 µm, p = 0.007). RNFL and GCIPL thicknesses showed no significant changes, except for minor sectoral variations. Steeper keratometry values correlated with lower QI in both conditions. Conclusions: SCLs enhanced posterior OCT scan quality while reducing anterior segment image clarity. These findings suggest that SCLs not only provide visual rehabilitation but also facilitate more reliable posterior segment imaging in keratoconus patients, despite mild interference with anterior segment OCT metrics. Further prospective studies are warranted to validate these results. Full article

Background: Posterior capsular opacification (PCO) remains the most common long-term complication following cataract surgery. This correspondence investigates whether intraocular lens (IOL) fixation type influences PCO risk by comparing Nd:YAG capsulotomy rates between capsulotomy-fixated (FEMTIS) and conventional in-the-bag IOLs with similar material and edge profiles. Methods: A systematic review was conducted. Eligible studies reporting quantitative YAG rates at ≥3 months of follow-up were included. Results: FEMTIS IOLs demonstrated lower capsulotomy rates (3.1% at 12 months) compared to in-the-bag LENTIS lenses (4.7% at 12 months), despite identical optic designs and identical material. Conclusions: This suggests that capsulotomy fixation may promote closer capsule–optic contact and reduce the potential space for lens epithelial cell migration. While data are limited by study heterogeneity and follow-up duration, early evidence supports anterior fixation as a potential strategy to reduce PCO risk and improve long-term capsular clarity. Further prospective studies are warranted. Limitations include heterogeneous study designs, relatively short follow-up, and reliance on Nd:YAG capsulotomy as the sole endpoint. Full article

Addressing the planetary crisis associated with climate change, biodiversity loss, global pollution, and public health requires novel and holistic approaches. Here, we present the methodology and initial results of an experiment conducted in Rome within the framework of the National Biodiversity Future Center (NBFC) project, Spoke 6. The major objective of this study was to outline the planetary health approach as a lens to assess urban health. This transdisciplinary case study explored the relationship between urban traffic-related external exposome and pro-oxidative responses in humans and plants. This methodology is based on the integration of atmospheric dynamics modeling, state-of-the-art aerosol measurements, biomonitoring in human cohorts, in vitro cellular assays, and the assessment of functional trait markers in urban trees. The results indicate that short-term exposure to urban aerosols, even at low concentrations, triggers rapid oxidative and inflammatory responses in bronchial epithelial cells, modulates gene and miRNA expression, alters gut microbiota diversity, and induces functional trait changes in urban trees. This study also highlights the feedback mechanisms between vegetation and atmospheric conditions, emphasizing the role of urban greenery in modulating microclimate and exposure. The methodology and initial results presented here will be further analyzed in future studies to explore proof of a cause–effect relationship between short-term exposure to traffic-related environmental stressors in urban areas and oxidative stress in humans and plants, with implications for chronic responses. In a highly urbanized world, this evidence could be pivotal in motivating the widespread implementation of planetary health approaches for assessing urban health. Full article

Background/Objectives: To investigate microRNA (miRNA) expression profiles in the anterior lens capsules of patients with glucocorticoid-induced cataracts (GIC) and to identify miRNAs potentially associated with glucocorticoid (GC) exposure and posterior subcapsular cataract (PSC) formation. Methods: A total of 33 participants were divided into four groups based on their GC usage history and cataract type: GIC (n = 10), age-related PSC (n = 6), GC-treated age-related cataract (ARC) (n = 7), and normal control (n = 10). Anterior lens capsule samples were obtained during cataract surgery and total RNA was extracted for quantitative real-time polymerase chain reaction (qRT-PCR). The expression levels of 12 selected miRNAs were quantified using a customized miScript miRNA PCR array. Results: Among the twelve miRNAs analyzed, seven (let-7a-5p, let-7d-5p, miR-15a-5p, miR-16-5p, miR-23b-3p, miR-26a-5p, and miR-125a-5p) were significantly differentially expressed among the groups (p < 0.05). In the GIC group, let-7a-5p, miR-23b-3p, miR-26a-5p, and miR-125a-5p were significantly upregulated, whereas let-7d-5p, miR-15a-5p and miR-16-5p were significantly downregulated compared to that in the normal control group. No significant differences in miRNA expression were observed between the GIC and age-related PSC groups or between the GIC and GC-treated ARC groups. Conclusions: This study demonstrates distinct miRNA expression patterns in the anterior lens capsules of patients with GIC. Altered expression of specific miRNAs may be linked to the pathogenesis of GC-induced PSC formation. These findings provide a molecular basis for further investigation into the regulatory roles of miRNAs in GC-associated cataracts. Full article

Background/Objectives: Oxidative stress plays a critical role in the development of ocular diseases such as cataracts. Selenium nanoparticles (SeNPs) offer antioxidant benefits with low toxicity. This study aimed to evaluate the antioxidant activity of SeNPs coated with D-α-tocopheryl polyethylene glycol succinate (TPGS) in human lens epithelial (HLE) cells. Methods: SeNPs were synthesised by reducing sodium selenite with ascorbic acid in the presence of TPGS. Physicochemical characterisation was carried out using dynamic light scattering to assess size and surface charge. Antioxidant activity was measured by a 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. Cytocompatibility was assessed on adult retinal pigment epithelial (ARPE-19) and HLE cells using PrestoBlue. Functional antioxidant performance was determined through enzymatic assays for glutathione peroxidase (GPx), thioredoxin reductase (TrxR), and glutathione (GSH), and lipid peroxidation was assessed using malondialdehyde (MDA) quantification. Catalase mimicry was evaluated under 3-amino-1,2,4-triazole (3-AT)-induced inhibition. Results: The optimal SeNP formulation had an average hydrodynamic diameter of 44 ± 3 nm, low PDI (<0.1), and a surface charge of −15 ± 3 mV. These TPGS-SeNPs demonstrated strong radical scavenging (EC₅₀ ≈ 1.55 µg/mL) and were well tolerated by ARPE-19 cells (IC₅₀ = 524 µg/mL), whereas HLE cells had a narrower biocompatibility window (≤0.4 µg/mL, IC₅₀ = 2.2 µg/mL). Under oxidative stress, SeNPs significantly enhanced GPx and TrxR activity but did not affect GSH or MDA levels. No catalase-mimetic activity was observed. Conclusions: TPGS-SeNPs exhibit potent antioxidant enzyme modulation under stress conditions in HLE cells. Although not affecting all oxidative markers, these nanoparticles show promise for non-invasive strategies targeting lens-associated oxidative damage, including cataract prevention. Full article

Posterior capsule opacification (PCO), a frequent complication of cataract surgery, arises from dysregulated wound healing and fibrotic transformation of residual lens epithelial cells. While transcriptomic and machine learning (ML) approaches have elucidated fibrosis-related pathways in other tissues, the molecular divergence between regenerative and fibrotic outcomes in the lens remains unclear. Here, we used an ex vivo chick lens injury model to simulate post-surgical conditions, collecting RNA from lenses undergoing either regenerative wound healing or fibrosis between days 1–3 post-injury. Bulk RNA sequencing data were normalized, log-transformed, and subjected to univariate filtering prior to training LASSO, SVM, and RF ML models to identify discriminatory gene signatures. Each model was independently validated using a held-out test set. Distinct gene sets were identified, including fibrosis-associated genes (VGLL3, CEBPD, MXRA7, LMNA, gga-miR-143, RF00072) and wound-healing-associated genes (HS3ST2, ID1), with several achieving perfect classification. Gene Set Enrichment Analysis revealed divergent pathway activation, including extracellular matrix remodeling, DNA replication, and spliceosome associated with fibrosis. RT-PCR in independent explants confirmed key differential expression levels. These findings demonstrate the utility of supervised ML for discovering lens-specific fibrotic and regenerative gene features and nominate biomarkers for targeted intervention to mitigate PCO. Full article

Several soluble mediators are activated during myogenesis and progression, and severe neurodegeneration, with related biomarkers, characterizes high myopia-related retinal atrophy. Targets of oxidative stress, epigenetics and neurogenic inflammation have been reported in the prospecting of some bioindicators to mirror retinal insults occurring in high myopia. The aim of the present study was to assess the expression of a few selected biomarkers belonging to the neurotrophin (NGF and BDNF), oxidative (NO, KEAP1/NRF2), and epigenetic (DNMT3 and HD1) pathways. Sixty-five (65; 76.25 ± 9.40 years) specimens—aqueous, anterior capsule (AC), and lens epithelial cells (LEC)—were collected at the time of cataract surgery and used for ELISA (aqueous) and transcripts analysis (AC/LEC). Biosamples were grouped as emmetrope (23; 81.00 ± 6.70 years); myopia (24; 75.96 ± 7.30); and high (pathological) myopia (18; 70.56 ± 11.68 years), depending on axial length (AL) and refractive error (RE). Comparisons and correlations were carried out between myopic and high-myopic subgroups. NGF and BDNF were lowered in myopic samples; NGF and BDNF transcripts were differentially expressed in LEC, and their expression correlated positively with NGF and negatively with BDNF, with the expression of the αSMA phenotype. NGF and BDNF correlated negatively with NO and nitrites. Oxidative stress (iNOS/NOX1/NOX4 and KEAP1/NRF2) and epigenetic (DNMTα3/HD1) transcripts were upregulated in myopic LEC, compared with emmetropic ones. Herein, we prospect the contribution of NGF and BDNF in both neuroinflammation and neuroprotection occurring in this chronic disease. Full article

Mitogen-Activated Protein Kinase Kinase Kinase 1 (MAP3K1) is a key signaling molecule essential for eyelid closure during embryogenesis. In mice, Map3k1 knockout leads to a fully penetrant eye-open at birth (EOB) phenotype due to disrupted MAPK signaling, abnormal epithelial differentiation, and morphogenesis. To further explore the roles of MAP3K1 in ocular development, we generated a Cre-inducible gain-of-function transgenic mouse, designated as Map3k1^TG, and crossed it with Lens epithelial (Le)-Cre mice to drive MAP3K1 overexpression in developing ocular surface epithelium (OSE). Map3k1^TG;Le-Cre embryos exhibited ocular defects including premature eyelid closure, lens degeneration, and corneal edema. While corneal epithelial differentiation remained intact, the lens epithelium degenerated with lens formation compromised. Eyelid epithelium was markedly thickened, containing cells with aberrant keratin (K)14/K10 co-expression. Genetic rescue experiments revealed that Map3k1^TG;Le-Cre restored eyelid closure in Map3k1 knockout mice, whereas MAP3K1 deficiency attenuated the epithelial thickening caused by transgene expression. Mechanistically, MAP3K1 overexpression enhanced c-Jun phosphorylation in vivo and activated JNK-c-Jun, WNT, TGFβ, and Notch signaling and promoted keratinocyte proliferation and migration in vitro. These findings highlight a dose-sensitive role for MAP3K1 in regulating epithelial proliferation, differentiation, and morphogenesis during eyelid development. Full article

Mechanical ventilation, a lifesaving intervention for critically ill patients, can also cause ventilator-induced lung injury (VILI), which is related to its interplay with immune system. To explore this relationship, we established a model consisting of two subsystems: a lung immune response system (LIRS), elucidating the interactions between immune cells and epithelial cells within the pulmonary environment, and a tidal volume damage system (TVDS), quantifying alveolar epithelial damage by simulating the detrimental effects of mechanical ventilation across varying tidal volumes. The integrated framework presents a novel lens for examining the interplay between heterogeneous immunological capabilities and tidal volume. The model reveals distinct responses among the individuals with varying immune capacities when subjected to identical tidal volumes, manifesting in diverse outcomes for healthy epithelial cells (eh). Analysis of simulation results shows a weak correlation between initial immune cell variables and eh, and a stronger correlation between eh and baseline repair capacity. Furthermore, while the initial immune state of lung tissue moderately influences epithelial health, the heterogeneous and inherent immunological competence of the tissue plays a pivotal role in shaping the diverse patterns observed in the development and severity of VILI. This insight highlights the importance of tailoring therapeutic strategies to individual immunological profiles, thereby optimizing patient outcomes. Full article

Cataracts, the leading cause of blindness globally, are caused by oxidative stress and inflammation, which disrupt lens transparency due to increased accumulation of reactive oxygen species (ROS) as well as protein and DNA damage during aging. Using in vitro, ex vivo, and in vivo models, we determined the protective efficacy of N-acetylcysteine amide (NACA) against oxidative stress-induced and aging-induced cataractogenesis. We found that lens epithelial cells exposed to the oxidative stress inducers hydrogen peroxide (H₂O₂) or tert-butyl hydroperoxide showed significant ROS accumulation and reduced cellular viability. These effects were inhibited by NACA via the suppression of ROS and thioredoxin-interacting protein (Txnip) expression, a regulator of oxidative stress-related cellular damage and inflammation. In ex vivo lens experiments, NACA significantly reduced H₂O₂-induced lens opacity and preserved lens integrity. Similarly to NACA-treated lenses ex vivo, the integrity and opacity of aged mouse lenses, when topically instilled with NACA, were preserved and reduced, respectively, and are directly related to reduced Txnip and increased thioredoxin (Trx) expression levels. Overall, our findings demonstrated the protective ability of NACA to abate aberrant redox-active pathways, particularly the ROS/TRX/TXNIP axis, thereby preventing cataractogenesis and preserving eye lens integrity and ultimately impeding aging-related cataracts. Full article