Search Results (282)

Diabetic keratopathy (DK) is a common ocular complication of diabetes mellitus (DM), affecting almost half of all diabetic patients. It is characterized by delayed healing of epithelial wounds, reduced corneal sensitivity, and persistent epithelial defects, which, in turn, significantly impair vision and quality of life. The limited understanding of its pathogenesis and the lack of effective treatments highlight the urgent need for more physiologically relevant experimental models. The three-dimensional (3D) models currently available provide valuable information on the pathophysiology of DK, although none of them yet fully reproduce the diabetic corneal phenotype complex. After a brief overview of corneal anatomy, the present review aims to systematically analyze the current 3D in vitro models developed for the study of DK, in terms of tissue architecture, presence of diabetic stimuli, and ability to replicate pathological traits. Full article

(1) Background: Over the years, technology and space missions have advanced, although the development of potential functional food and food supplements must be improved for maintaining astronauts’ health and helping them overcome space-specific challenges during long missions. (2) Scope and approach: Using a review approach, this study aimed to investigate the potential of functional food to counteract radiation and microgravity spaceflight-related health problems. (3) Results: Microgravity and space radiation affect the body’s biochemical processes and increase levels of reactive oxygen species, which may lead to health problems, including musculoskeletal deconditioning, cardiovascular degeneration, disruptions in gastrointestinal health, ocular problems, alterations to the immune system, and hormonal imbalances, among others. In addition to medical care, functional food plays a key role as a countermeasure against space-induced physiological issues. Previous research showed that functional food rich in flavonoids, omega-3 fatty acids, vitamins, minerals, antioxidant compounds, proteins, probiotics, or prebiotics strengthens the immune system and reduces risks associated with long spaceflights, such as bone density loss, muscle atrophy, oxidative stress, and other health alterations. (4) Conclusions: Despite the fundamental role of functional food in spaceflights, the main challenges remain in preserving and packaging these foods to ensure their safety on long space missions. Future innovations include 3D food printing, space algae cultivation, and novel preservation technologies. Full article

Biological extracellular vesicles in tear fluids, such as exosomes, are thought to have physiological functions in the management of healthy ocular surface epithelium, including corneal epithelium. However, the physiological roles of tear extracellular vesicles in the ocular surface remain unclear. In this study, we investigated the physiological function of tear extracellular vesicles in mouse tear fluids in the ocular surface epithelium in vitro. Morphological analysis of the isolated extracellular vesicles from mouse tear fluids was performed using nanoparticle tracking analysis and transmission electron microscopy. The identified particles were characterised by immunoblotting for exosomal markers. After confirming the uptake of tear exosomes in cultured corneal epithelial cells, gene expression changes in mouse cultured corneal epithelial cells after tear exosome treatment were analysed. Immunostaining analysis was performed to confirm cell proliferation in the cultured corneal epithelial cells with tear exosome treatment. Tear fluids from mice contain nanoparticles with exosome-like morphologies, which express the representative exosomal markers CD9 and TSG101. The extracellular vesicles can be taken up by cultivated murine corneal epithelial cells in vitro and induce expression changes in genes related to the cell cycle, cell membranes, microtubules, and signal peptides. Treatment with the tear extracellular vesicles promoted cell proliferation of cultured murine corneal epithelial cells. Our study provides evidence that murine tear fluids contain extracellular vehicles like exosomes and they may contribute to the maintenance of the physiological homeostatic environment of the ocular surface. Full article

The eye, a complex organ essential for visual perception, is composed of diverse cell populations with specialized functions; however, the complex interplay between these cellular components and their underlying molecular mechanisms remains largely elusive. Traditional biotechnologies, such as bulk RNA sequencing and in vitro models, are limited in capturing cellular heterogeneity or accurately mimicking the complexity of human ophthalmic diseases. The advent of single-cell RNA sequencing (scRNA-seq) has revolutionized ocular research by enabling high-resolution analysis at the single-cell level, uncovering cellular heterogeneity, and identifying disease-specific gene profiles. In this review, we provide a review of scRNA-seq application advancement in ocular physiology and pathology, highlighting its role in elucidating the molecular mechanisms of various ocular diseases, including myopia, ocular surface and corneal diseases, glaucoma, uveitis, retinal diseases, and ocular tumors. By providing novel insights into cellular diversity, gene expression dynamics, and cell–cell interactions, scRNA-seq has facilitated the identification of novel biomarkers and therapeutic targets, and the further integration of scRNA-seq with other omics technologies holds promise for deepening our understanding of ocular health and diseases. Full article

Topical drug administration is a common method of delivering medications to the eye to treat various ocular conditions, including glaucoma, dry eye, and inflammation. Drug efficacy following topical administration, including the drug’s distribution within the eye, absorption and elimination rates, and physiological responses can be predicted using physiologically based pharmacokinetic (PBPK) modeling. High-resolution computational models of the eye are desirable to improve simulations of drug delivery; however, these approaches can have long run times. In this study, a fast-running computational quasi-3D (Q3D) model of the human tear film was developed to account for absorption, blinking, drainage, and evaporation. Visualization of blinking mechanics and flow distributions throughout the tear film were enabled using this Q3D approach. Average drug absorption throughout the tear film subregions was quantified using a high-resolution compartment model based on a system of ordinary differential equations (ODEs). Simulations were validated by comparing them with experimental data from topical administration of 0.1% dexamethasone suspension in the tear film (R² = 0.76, RMSE = 8.7, AARD = 28.8%). Overall, the Q3D tear film model accounts for critical mechanistic factors (e.g., blinking and drainage) not previously included in fast-running models. Further, this work demonstrated methods toward improved computational efficiency, where central processing unit (CPU) time was decreased while maintaining accuracy. Building upon this work, this Q3D approach applied to the tear film will allow for more seamless integration into full-body models, which will be an extremely valuable tool in the development of treatments for ocular conditions. Full article

Adeno-associated virus (AAV) vectors face a critical translational challenge in ocular gene therapy due to pre-existing neutralizing antibodies (NAbs) whose seroprevalence limits patient eligibility. Standard NAb detection using non-ocular cell models (Human Embryonic Kidney 293T) may inadequately predict retinal transduction inhibition due to cell type-related variations in receptor usage and immunogenicity. This study established parallel NAb detection platforms utilizing human retinal pigment epithelial (ARPE-19) cells and standard 293T cells to systematically evaluate clinical serum samples against ophthalmologically relevant AAV serotypes (2, 5, 8, 9) via luciferase reporter-based transduction inhibition assays. Comparative analysis demonstrated ARPE-19 exhibited 42–48% higher NAb titers against AAV5/9 compared to 293T cells, with distinct serotype-biased neutralization hierarchies observed between cellular models. Furthermore, female-derived sera exhibited significantly elevated NAbs against particular serotypes in the ARPE-19 system. Critically, inter-serotype cross-neutralization correlation patterns differed substantially between cellular platforms. These findings demonstrate that physiologically relevant retinal cellular models provide essential immunological profiling data, revealing NAb characteristics obscured in standard assays. Consequently, employing retinal cell-based platforms is crucial for optimizing AAV serotype selection, patient stratification, and predicting clinical outcomes in ocular gene therapy. Full article

The One Health approach is rapidly gaining the attention of the scientific community worldwide and is expected to be a major model of scientific reasoning in the 21st century, concerning medical, veterinary and environmental issues. The basic concept of One Health, that humans, animals and their environments are parts of the same natural world affecting each other, is rooted in most ethnic as well as in many religious traditions. Despite this unity and for historical reasons, medical, veterinary and environmental sciences developed independently. The One Health concept tries to reunite these and many other relevant sciences, aiming at a deeper understanding of the interconnection between the natural world, humans and animal health. The dynamic interplay between a host’s microbiome, the microbiomes of other hosts, and environmental microbial communities profoundly influences the host health, given the essential physiological functions the microbiome performs within the organism. The biodiversity of microbiomes is broad and complex. The different areas of the skin, the upper and lower respiratory systems, the ocular cavity, the oral cavity, the gastrointestinal tract and finally the urogenital system of pets and humans alike are niches where a multitude of microorganisms indigenous and transient—commensals and pathogens, thrive in a dynamic antagonistic balance of populations of different phyla, orders, genera and species. The description of these microbiomes attempted in this article is not meant to be exhaustive but rather demonstrative of their complexity. The study of microbiomes is a necessary step towards the One Health approach to pets and humans. Yet, despite the progress made on that subject, the scientific community faces challenges, such as the limitations of studies performed, the scarcity of studies concerning the microbiomes of cats, the multitude of environmental factors affecting the results and others. The two new terms proposed in this article, the “familiome” and the “oikiome”, will aid in the One Health theoretical analysis as well as in its practical approach. The authors strongly believe that new technological breakthroughs, like Big Data Analytics and Artificial Intelligence (AI), will significantly help to overcome these hazards. Full article

Spaceflight-associated dry eye syndrome (SADES) has been reported among astronauts during both International Space Station (ISS) and Space Transportation System (STS) missions. As future missions extend beyond low Earth orbit, the physiological challenges of spaceflight include microgravity, radiation, and environmental stressors, which may further exacerbate the development of ocular surface disease. A deeper understanding of the underlying pathophysiology, along with the exploration of innovative countermeasures, is critical. In this review, we examine nanomedicine as a promising countermeasure for managing ophthalmic conditions in space, with the goal of enhancing visual health and mission readiness for long-duration exploration-class missions. Full article

The therapeutic potential of exosomes (Exos), a subpopulation of extracellular vesicles (EVs) secreted by various cell types, has been broadly emphasized. Exos are endosome-derived membrane-bound vesicles 50–150 nm in size. Exos can be general or cell type-specific. Their contents enable them to function as multi-signaling and vectorized vehicles. Exos are important for maintaining cellular homeostasis. They are released into extracellular spaces, leading to uptake by neighboring or distant cells and delivering their contents to modulate cell signaling. Exos influence tissue responses to injury, infection, and disease by fusion with the target cells and transferring their cargo, including cytokines, growth and angiogenic factors, signaling molecules, lipids, DNA, mRNAs, and non-coding RNAs. They are implicated in various physiological and pathological conditions, including ocular surface events, such as corneal scarring, wound healing, and inflammation. Their biocompatibility, stability, low immunogenicity, and easy detectability in bodily fluids (blood, tears, saliva, and urine) make them promising tools for diagnosing and treating ocular diseases. The potential to engineer specific Exo cargos makes them outstanding therapeutic delivery vehicles. The objective of this review is to provide novel insights into the functions of Exo cargos and their applications as biomarkers and therapeutics, or targets in the cornea. Full article

Pericytes, specialized mural cells surrounding microvessels, play a crucial role in maintaining vascular homeostasis and function across various organs, including the eye. These versatile cells regulate blood flow, support the integrity of the blood–retinal barrier, and contribute to angiogenesis. Recent advancements in molecular and cellular biology have revealed the heterogeneity of pericytes and their critical involvement in ocular physiology and pathology. This review provides a comprehensive analysis of pericyte functions in ocular health and their implications in diseases such as diabetic retinopathy, age-related macular degeneration, glaucoma, and retinal vein occlusion. Pericyte dysfunction is implicated in vascular instability, neurovascular coupling failure, inflammation, and pathological neovascularization, contributing to vision-threatening disorders. The review further explores recent findings on pericyte-targeted therapies, including pharmacological agents, gene therapy, and cell-based approaches, aiming to restore pericyte function and preserve ocular health. Full article

Background: The biomechanical properties of ocular tissues are critical to physiological processes that span ocular development, aging, and disease. The structural integrity of these tissues is important in mediating how the eye responds to strain and stress that pose challenges to physiological homeostasis. In the posterior segment, the peripapillary sclera and lamina separate the intraocular chamber and the fluid-filled subarachnoid space. Degradation of each contribute to pathogenic progression in multiple conditions and are largely determined by the integrity and architecture of collagen fibers, especially type I collagen. Methods: We used atomic force microscopy to measure how stress induced by elevations in intraocular pressure impacts stiffness of the peripapillary sclera and glial lamina in the rat eye and whether changes in stiffness could be influenced by topical treatment of a reparative mimetic of type I collagen. Results: Four weeks of elevated intraocular pressure reduced Young’s modulus in peripapillary sclera and glial lamina, coincident with reduced anterograde transport along the optic projection to the brain. Reduction in tissue stiffness correlated with an increase in fragmented collagen. Topical application of collagen mimetic peptide during the period of elevation countered both. Conclusions: Collagen remodeling occurs in many ocular conditions that influence the peripapillary sclera and glial lamina, including glaucoma and myopia. Our results suggest that topical application of collagen mimetic peptides that intercalate with and repair collagen damaged by disease processes could serve to mitigate changes in tissue stiffness and integrity due to degraded collagen. Full article

Ocular drug delivery presents a persistent clinical challenge due to the protective anatomical structure of the eye, physiological barriers such as reflex blinking, and continuous tear fluid turnover. These factors significantly limit the bioavailability of topically applied medications, reducing the therapeutic effectiveness of conventional formulations, such as eye drops, ointments, and suspensions, particularly in the management of chronic ocular disorders, including dry eye syndrome, diabetic retinopathy, and age-related macular degeneration. Drug-eluting contact lenses (DECLs) offer a promising alternative, enabling sustained, localized, and controlled drug release directly at the ocular surface. While several reviews have addressed contact lenses as drug delivery platforms, this work provides a distinct perspective by focusing specifically on biodegradable polymer-based systems. Emphasis is placed on recent advances in the design and fabrication of DECLs using natural and synthetic biodegradable polymers, which offer superior biocompatibility, customizable degradation kinetics, and the capacity for programmable drug release. This review discusses the selection criteria for polymer matrices, strategies for drug incorporation, and key factors influencing release profiles. Moreover, this study highlights innovative methodologies and therapeutic approaches that differentiate it from the existing literature, providing a timely and comprehensive resource for researchers developing next-generation polymeric ocular drug delivery systems. Full article

Pregnancy orchestrates profound neurological, hormonal, and anatomical transformations in the maternal brain, preparing it for caregiving and infant bonding. Neuroimaging reveals structural changes such as gray matter reductions and white matter reorganization during pregnancy, followed by partial recovery postpartum. These adaptations are modulated by fluctuating levels of estradiol, progesterone, prolactin, and oxytocin, which coordinate neuroplasticity and behavioral readiness. At the molecular and cellular levels, pregnancy hormones drive synaptic remodeling, neurogenesis, and glial activity. Together, these changes support maternal motivation, attachment, and responsiveness, highlighting the maternal brain’s dynamic plasticity across gestation and the postpartum period. Also, pregnancy induces profound physiological changes, particularly in vascular, hormonal, and neurologic systems, to support maternal and fetal health. While these adaptations are essential, they can predispose pregnant individuals to various neurologic and ophthalmic pathologies. This review explores how pregnancy-related changes—including hypercoagulability, pituitary enlargement, hormonal fluctuations, and immunological modulation—contribute to conditions such as stroke, idiopathic intracranial hypertension, preeclampsia-associated visual disturbances, and demyelinating disorders like neuromyelitis optica spectrum disorder and multiple sclerosis. Additionally, ocular manifestations of systemic diseases like diabetic retinopathy and thyroid orbitopathy are discussed. Understanding these complex interactions is critical for prompt recognition, accurate diagnosis, and appropriate management of vision-threatening and neurologically significant complications during pregnancy. Nevertheless, many aspects of physiological and pathological changes during and after pregnancy remain unknown and warrant further investigation. Full article

Background/Objectives: The management of ocular tumours is faced with the challenge of developing a suitable treatment strategy with consideration of the anatomical and physiological protective barriers of the eye. Interferon alpha has been employed to treat patients with ocular tumours for decades; however, its short half-life and poor tolerability necessitate frequent administration. This study focuses on the design of an injectable pH-responsive and protective nanoparticle system dispersed into a thermo-responsive hydrogel for site-specific sustained delivery of interferon alpha (IFN-α2b) in the treatment of ocular surface tumours. Methods: The synthesis of a poly(ethylene glycol)-poly(caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG) triblock copolymer (PECE) was undertaken. The IFN-α2b was encapsulated in poly(β-amino ester) (PBAE) nanoparticles (NP) with pH-responsive characteristics to proposedly release the IFNα-2b in response to the acidic nature of the tumour microenvironment. This was followed by characterisation via Fourier transform infrared spectroscopy (FT-IR), ¹H-nuclear magnetic resonance (¹H-NMR) analysis, differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD) analysis, thermogravimetric analysis (TGA), and thermal-transition analysis of the PECE hydrogels. Results: Release studies demonstrated that the PBAE nanoparticulate PEG-PCL-PEG hydrogel was both pH-responsive, while providing controlled release of IFN-α2b, and thermo-responsive. Release analysis highlighted that IFN-α2b-loaded NP dispersed into the hydrogel (IFNH) further prolonged the release of IFN-α2b with a pH-responsive yet controlled release rate in an acidic environment simulating a tumour microenvironment. The developed system proved to be biocompatible with human retinal pigment epithelial cells and the released IFN-α demonstrated bioactivity in the presence of an A172 glioblastoma cell line. Conclusions: In conclusion, the PECE hydrogel has promising potential for application as an ocular drug delivery system for the treatment of ocular tumours and could potentially overcome and prevent the drawbacks associated with the commercially available IFN-α2b injection. Full article

As a forward-looking development in air traffic control (ATC), remote towers rely on virtualized information presentation, which may exacerbate visual fatigue among controllers and compromise operational safety. This study proposes a visual fatigue recognition model based on multimodal physiological signals. A 60-min simulated remote tower task was conducted with 36 participants, during which eye-tracking (ET), electroencephalography (EEG), electrocardiography (ECG), and electrodermal activity (EDA) signals were collected. Subjective fatigue questionnaires and objective ophthalmic measurements were also recorded before and after the task. Statistically significant features were identified through paired t-tests, and fatigue labels were constructed by combining subjective and objective indicators. LightGBM was then employed to rank feature importance by integrating split frequency and information gain into a composite score. The top 12 features were selected and used to train a multilayer perceptron (MLP) for classification. The model achieved an average balanced accuracy of 0.92 and an F1 score of 0.90 under 12-fold cross-validation, demonstrating excellent predictive performance. The high-ranking features spanned four modalities, revealing typical physiological patterns of visual fatigue across ocular behavior, cortical activity, autonomic regulation, and arousal level. These findings validate the effectiveness of multimodal fusion in modeling visual fatigue and provide theoretical and technical support for human factor monitoring and risk mitigation in remote tower environments. Full article