Ocular Physiology Research Articles

The Role of Reactive Oxygen Species in Age-Related Macular Degeneration: A Comprehensive Review of Antioxidant Therapies.

This review article delves into the intricate roles of reactive oxygen species (ROS) in the pathogenesis of age-related macular degeneration (AMD). It presents a detailed analysis of the oxidative stress mechanisms that contribute to the development and progression of these diseases. The review systematically explores the dual nature of ROS in ocular physiology and pathology, underscoring their essential roles in cellular signaling and detrimental effects when in excess. In the context of AMD, the focus is on the oxidative impairment in the retinal pigment epithelium and Bruch's membrane, culminating in the deterioration of macular health. Central to this review is the evaluation of various antioxidant strategies in the prevention and management of AMD. It encompasses a wide spectrum of antioxidants, ranging from dietary nutrients like vitamins C and E, lutein, and zeaxanthin to pharmacological agents with antioxidative properties. The review also addresses novel therapeutic approaches, including gene therapy and nanotechnology-based delivery systems, aiming to enhance antioxidant defense mechanisms in ocular tissues. The article concludes by synthesizing current research findings, clinical trial data, and meta-analyses to provide evidence-based recommendations. It underscores the need for further research to optimize antioxidant therapies, considering individual patient factors and disease stages. This comprehensive review thus serves as a valuable resource for clinicians, researchers, and healthcare professionals in ophthalmology, offering insights into the potential of antioxidants in mitigating the burden of AMD.

Clinical Ocular Exposure Extrapolation for a Complex Ophthalmic Suspension Using Physiologically Based Pharmacokinetic Modeling and Simulation.

The development of generic ophthalmic drug products with complex formulations is challenging due to the complexity of the ocular system and a lack of sensitive testing to evaluate the interplay of its physiology with ophthalmic drugs. New methods are needed to facilitate the development of ophthalmic generic drug products. Ocular physiologically based pharmacokinetic (O-PBPK) models can provide insight into drug partitioning in eye tissues that are usually not accessible and/or are challenging to sample in humans. This study aims to demonstrate the utility of an ocular PBPK model to predict human exposure following the administration of ophthalmic suspension. Besifloxacin (Bes) suspension is presented as a case study. The O-PBPK model for Bes ophthalmic suspension (Besivance® 0.6%) accounts for nasolacrimal drainage, suspended particle dissolution in the tears, ocular absorption, and distribution in the rabbit eye. A topical controlled release formulation was used to integrate the effect of Durasite® on Bes ocular retention. The model was subsequently used to predict Bes exposure after its topical administration in humans. Drug-specific parameters were used as validated for rabbits. The physiological parameters were adjusted to match human ocular physiology. Simulated human ocular pharmacokinetic profiles were compared with the observed ocular tissue concentration data to assess the OCAT models' ability to predict human ocular exposure. The O-PBPK model simulations adequately described the observed concentrations in the eye tissues following the topical administration of Bes suspension in rabbits. After adjustment of physiological parameters to represent the human eye, the extrapolation of clinical ocular exposure following a single ocular administration of Bes suspension was successful.

Physiological Effects of Soat1 Inactivation on Homeostasis of the Mouse Ocular Surface.

Soat1/SOAT1 have been previously reported to be critical for the biosynthesis of cholesteryl esters (CEs) in the mouse Meibomian glands (MGs) as the loss of function led to an arrest of CE production and a substantial accumulation of nonesterified cholesterol in the meibum, causing an increase in its melting temperature. The purpose of this study was to further investigate the role of Soat1 in meibogenesis and ocular surface physiology. The mouse ocular features of knockout Soat1-/- and wild type (WT) mice were studied using various ophthalmic and histological techniques, mouse lipidomes were monitored using liquid chromatography/mass spectrometry, whereas their transcriptomes were compared to characterize the effects of the mutation on the gene expression profiles in the MG and cornea. Soat1-/- mice displayed increased tear production and severe corneal abnormalities, such as corneal thinning, (neo)vascularization, ulceration, and opacification that progressed with aging. Transcriptomic analyses led to identification of a range of significantly disrupted pathways, which included general and specific lipid metabolism-related pathways, keratinization, angiogenesis/(neo)vascularization, muscle contraction, and several other pathways. In addition, histological and histochemical experiments revealed morphological changes in the MG, cornea, and conjunctiva in Soat1-/- mice. Notably, the mRNA microarray expression level of Soat1 in WT MGs (log2 17.5) was 1000 × of that in the mouse cornea (log2 7.5). These findings suggest a direct involvement of Soat1/SOAT1 in MGs in maintaining ocular surface homeostasis, in general, and corneal health, specifically.

Ayurvedic Management of Shushkakshipaka w.s.r. To Dry Eye Syndrome - A Single Case Study

Eyes are one of the most powerful tools that anyone can have; hence, all efforts should be made to protect the eyes. In today’s era, people depend more on machines like computers in all sectors of life. These cause some heat and radiation which certainly causes ill effects on the eyes. Tear (Ashru) secretion is an integral component of the ocular surface physiology; when compromised (quantitatively or qualitatively) leads to shushkakshipaka (dry eye syndrome) with various ocular discomfort symptoms and ultimately the patient may land in corneal blindness. Local, systemic, and environmental factors majorly affect its pathogenesis. Vata and Pitta/Rakta vitiation as per Ayurvedic viewpoint are the major contributing pathological factors in its manifestation. A 28-year-old female patient approached Shalakya OPD of SKGAC and H, Kurukshetra, complaining of irritation, foreign body sensation, eye fatigue, and pain in the periorbital region along with a feeling of dryness for 1 year. The patient had slight symptomatic relief but when medications were discontinued the condition used to reoccur, so she turned to Ayurvedic treatment for relief. In Ayurveda classics, specific treatment has been mentioned for Shushkakshipaka such as Snehana (~in-take of Ghee), Tarpana (~retention of ghee over eyes), Nasya (~Nasal medication), and Pariseka (~ocular irrigation). A patient of shushkakshipaka was treated with such treatment protocol, is presented as a case study in this article. Contrary to the available modern medical treatment Ayurveda propounds a systematic approach in the treatment of dry eye syndrome.

Two-Photon and Multiphoton Microscopy in Anterior Segment Diseases of the Eye.

Two-photon excitation microscopy (TPM) and multiphoton fluorescence microscopy (MPM) are advanced forms of intravital high-resolution functional microscopy techniques that allow for the imaging of dynamic molecular processes and resolve features of the biological tissues of interest. Due to the cornea's optical properties and the uniquely accessible position of the globe, it is possible to image cells and tissues longitudinally to investigate ocular surface physiology and disease. MPM can also be used for the in vitro investigation of biological processes and drug kinetics in ocular tissues. In corneal immunology, performed via the use of TPM, cells thought to be intraepithelial dendritic cells are found to resemble tissue-resident memory T cells, and reporter mice with labeled plasmacytoid dendritic cells are imaged to understand the protective antiviral defenses of the eye. In mice with limbal progenitor cells labeled by reporters, the kinetics and localization of corneal epithelial replenishment are evaluated to advance stem cell biology. In studies of the conjunctiva and sclera, the use of such imaging together with second harmonic generation allows for the delineation of matrix wound healing, especially following glaucoma surgery. In conclusion, these imaging models play a pivotal role in the progress of ocular surface science and translational research.

AHP DB: a reference database of proteins in the human aqueous humor.

The aqueous humor (AH) is a low-viscosity biofluid that continuously circulates from the posterior chamber to the anterior chamber of the eye. Recent advances in high-resolution mass-spectrometry workflows have facilitated the study of proteomic content in small-volume biofluids like AH, highlighting the potential clinical implications of the AH proteome. Nevertheless, in-depth investigations into the role of AH proteins in ocular diseases have encountered challenges due to limited accessibility to these workflows, difficulties in large-scale AH sample collection and the absence of a reference AH proteomic database. In response to these obstacles, and to promote further research on the involvement of AH proteins in ocular physiology and pathology, we have developed the web-based Aqueous Humor Proteomics Database (AHP DB). The current version of AHP DB contains proteomic data from 307 human AH samples, which were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The database offers comprehensive information on 1683 proteins identified in the AH samples. Furthermore, relevant clinical data are provided for each analyzed sample. Researchers also have the option to download these datasets individually for offline use, rendering it a valuable resource for the scientific community. Database URL: https://ahp.augusta.edu/.

Synergism between coexisting eye diseases and sex in increasing the prevalence of the dry eye syndrome

The aim was to investigate prevalence of dry eye syndrome (DES) in a population-based sample in Germany. The association between coexisting eye diseases and DES was also of interest. We recontacted participants of the Heinz Nixdorf Recall study between 2018 and 2021 by postal questionnaire that included the Women’s Health Study questionnaire on DES. We estimated prevalence of DES and examined DES-associated factors among 2095 participants aged 62–91 years. We performed interaction analyses between sex and coexisting eye diseases in relation to the DES prevalence and performed bias analyses to examine the robustness of the results. The DES prevalence was 31.5% (34–36% after correction for potential non-response bias, 24.1% after correction for outcome misclassification) and it was almost 2.1-times higher in women than in men (women 42.3%, men 20.4%). Among DES subjects, 70.3% had received treatment in the previous 12 months. There was synergism between female sex and coexisting eye diseases (cataract, glaucoma, macular degeneration) in terms of DES prevalence. The extrapolated numbers of patients aged 62–91 years with DES in Germany are 1.1–1.3 million men and 6.1–6.8 million women. The observed synergism may be explained by differences in ocular physiology, subjective perception and response behavior. Women with eye diseases (cataract, glaucoma, macula degeneration) appear to have a markedly higher susceptibility to suffer from DES than men, so that a diagnostic workup of DES symptoms is particularly justified in women with these eye diseases.

Climate Change and Ocular Surface Disease Epidemic

Climate change offers several difficulties to global health, including a considerable influence on ophthalmology. Ocular surface disorders (OSDs) refer to a group of ailments that affect the cornea, conjunctiva, and tear film, with dry eye syndrome (DES) being the most common. Various environmental variables, such as increasing temperatures, changed humidity levels, and increased airborne contaminants, are thought to exacerbate OSDs in response to changing climate conditions. These environmental stresses have a direct impact on ocular physiology, resulting in tear film instability, epithelium damage, and inflammation. Climate change’s rising temperatures, changing precipitation patterns, and increased frequency of extreme weather events all have serious consequences for ocular surface disorders. The intricate relationship between climate change and the epidemiology of OSDs, with a focus on how environmental factors such as heatwaves, air pollution, and allergen distribution influence the prevalence and severity of diseases such as dry eye syndrome, allergic conjunctivitis, and other ocular surface diseases.

Tear‐borne interleukin 1‐beta and transforming growth factor‐beta and its relationship with clinical parameters in neophytes contact lens wearers

Aims/Purpose: To determine the presence of Interleukin 1‐beta (IL1‐β) and Transforming growth factor‐beta (TGF‐β) in the tears of neophytes contact lens wearers; and investigate the relationship between their concentration, tear stability, and ocular physiology findings.Methods: In this clinical trial, 12 neophytes (5 males, 24.0 ± 5.0 years) were dispensed with delefilcon A contact lenses. Physiological responses (bulbar and limbal hyperemia), non‐invasive tear break‐up times, and tear sample collections were obtained in the morning (before lens insertion; 9–10 a.m.) and afternoon (before lens removal; 7–8 p.m.) of the same day. The tear samples were assayed for IL1‐β and TGF‐β concentrations using Enzyme‐Linked Immunoabsorbent Assay kits. A parallel control group of 11 individuals (6 males, 25.0 ± 5.0) was also assessed to determine the levels of the biomarkers in the tears of non‐contact lens wearers.Results: Patients wore lenses for an average of 7:20 [6,9] h. Bulbar and limbal hyperemia increased throughout the day (p < 0.001). Tear break‐up times were lower in the afternoon compared to the morning assessment (4.7 ± 2.0 Vs. 12.2 ± 8.8 seconds; p < 0.001). The IL1‐β levels were higher in neophytes compared to controls (3.2 ± 4.7 Vs. 0.1 ± 0.1 ρg/ml; p = 0.05) but only in the afternoon. A significant correlation was found between IL1‐β concentration, bulbar (r = 0.405, p = 0.008), and limbal hyperemia (r = 0.499, p = 0.027) in the morning period. No substantial changes were reported for TGF‐β.Conclusions: The use of contact lenses might alter the IL1‐β regulatory mechanisms and disturb ocular surface homeostasis. However, more clinical evidence is needed to understand this phenomenon.

Basic concepts of exercise physiology for the vision and eye research community

The epidemiology of the second half of the 20th century has been marked by a transition from infectious to non‐communicable diseases. Instead of having a unique etiological cause, the non‐communicable diseases are believed to develop by the temporal confluence of several risk factors on a given individual. Risk factors of genetic origin are considered non‐modifiable nowadays. In contrast, behavioural risk factors, including lifestyle, are considered modifiable, and, therefore the preventive and adjuvant interventions aimed to reduce the risk or modify the natural course of non‐communicable diseases are based in lifestyle changes.Since the seminal work of Jeremy Morris in the 50's (the so‐called “London Bus Study”) epidemiological evidences have been accumulating over time on the potential role of a reduced physical activity in every domain of daily life as a risk factor for several non‐modifiable diseases. This is aggravated by the progressive trend of a reduced physical activity performed by the worldwide population during the last decades. The relationship of physical inactivity and/or sedentarism with several systemic diseases is clearly proven nowadays, and the underlying pathophysiological explanations are starting to be understood.In contrast what it happens in other organs or systems the potential effects of physical activity on ocular physiology and/or pathophysiology are still almost unknown. The design and development of future studies focused on these topics would need that the eye and vision research community is familiarized with: a) the current terminology on the field of physical activity and exercise; b) the hormetic properties of exercise, and consequently, the differences among acute responses and chronic adaptations to it; and, c) the potential physiological mechanisms ‐ranging from classical neuroendocrine responses to the recent concept of exerquines‐ that may explain them. All of them will be presented and discussed at this talk.

A Standardized Protocol for Extraction and Homogenization of Ocular Tissues.

The eye is a complex organ composed of multiple tissues in anterior and posterior eye segments. Malfunctions of any of these tissues can lead to ocular diseases and loss of vision. A detailed understanding of the ocular anatomy and physiology in animal models and humans contributes to the development of ocular drugs by enabling studies on drug delivery and clearance routes, pharmacokinetics, and toxicity. This protocol provides step-by-step instructions for the extraction and homogenization of ocular tissues for enzymatic and proteomics analyses. Key features • Suitable protocol for the extraction and isolation of ocular tissue from humans and laboratory animals (rabbit, pig, rat, mouse) while minimizing cross-contamination. • Hard or soft tissue homogenates can be prepared efficiently using a Bead Ruptor homogenizer. • Allows to determine the protein contents in prepared homogenates.

Fibrous finite element modeling of the optic nerve head region

The optic nerve head (ONH) region at the posterior pole of the eye is supported by a fibrous structure of collagen fiber bundles. Discerning how the fibrous structure determines the region biomechanics is crucial to understand normal physiology, and the roles of biomechanics on vision loss. The fiber bundles within the ONH structure exhibit complex three-dimensional (3D) organization and continuity across the various tissue components. Computational models of the ONH, however, usually represent collagen fibers in a homogenized fashion without accounting for their continuity across tissues, fibers interacting with each other and other fiber-specific effects in a fibrous structure. We present a fibrous finite element (FFE) model of the ONH that incorporates discrete collagen fiber bundles and their histology-based 3D organization to study ONH biomechanics as a fibrous structure. The FFE model was constructed using polarized light microscopy data of porcine ONH cryosections, representing individual fiber bundles in the sclera, dura and pia maters with beam elements and canal tissues as continuum structures. The FFE model mimics the histological in-plane orientation and width distributions of collagen bundles as well as their continuity across different tissues. Modeling the fiber bundles as linear materials, the FFE model predicts the nonlinear ONH response observed in an inflation experiment from the literature. The model also captures important microstructural mechanisms including fiber interactions and long-range strain transmission among bundles that have not been considered before. The FFE model presented here advances our understanding of the role of fibrous collagen structure in the ONH biomechanics. Statement of SignificanceThe microstructure and mechanics of the optic nerve head (ONH) are central to ocular physiology. Histologically, the ONH region exhibits a complex continuous fibrous structure of collagen bundles. Understanding the role of the fibrous collagen structure on ONH biomechanics requires high-fidelity computational models previously unavailable. We present a computational model of the ONH that incorporates histology-based fibrous collagen structure derived from polarized light microscopy images. The model predictions agree with experiments in the literature, and provide insight into important microstructural mechanisms of fibrous tissue biomechanics, such as long-range strain transmission along fiber bundles. Our model can be used to study the microstructural basis of biomechanical damage and the effects of collagen remodeling in glaucoma.

Circadian rhythm, ipRGCs, and dopamine signalling in myopia.

Myopia, a common ophthalmic disorder, places a high economic burden on individuals and society. Genetic and environmental factors influence myopia progression; however, the underlying mechanisms remain unelucidated. This paper reviews recent advances in circadian rhythm, intrinsically photosensitive retinal ganglion cells (ipRGCs), and dopamine (DA) signalling in myopia and proposes the hypothesis of a circadian rhythm brain retinal circuit in myopia progression. The search of relevant English articles was conducted in the PubMed databases until June 2023. Based on the search, emerging evidence indicated that circadian rhythm was associated with myopia, including circadian genes Bmal1, Cycle, and Per. In both humans and animals, the ocular morphology and physiology show rhythmic oscillations. Theoretically, such ocular rhythms are regulated locally and indirectly via the suprachiasmatic nucleus, which receives signal from the ipRGCs. Compared with the conventional retinal ganglion cells, ipRGCs can sense the presence of light because of specific expression of melanopsin. Light, together with ipRGCs and DA signalling, plays a crucial role in both circadian rhythm and myopia. In summary, regarding myopia progression, a circadian rhythm brain retinal circuit involving ipRGCs and DA signalling has not been well established. However, based on the relationship between circadian rhythm, ipRGCs, and DA signalling in myopia, we hypothesised a circadian rhythm brain retinal circuit.

Posterior corneoscleral limbus: Architecture, stem cells, and clinical implications.

The limbus is a transition from the cornea to conjunctiva and sclera. In human eyes, this thin strip has a rich variation of tissue structures and composition, typifying a change from scleral irregularity and opacity to corneal regularity and transparency; a variation from richly vascularized conjunctiva and sclera to avascular cornea; the neural passage and drainage of aqueous humor. The limbal stroma is enriched with circular fibres running parallel to the corneal circumference, giving its unique role in absorbing small pressure changes to maintain corneal curvature and refractivity. It contains specific niches housing different types of stem cells for the corneal epithelium, stromal keratocytes, corneal endothelium, and trabecular meshwork. This truly reflects the important roles of the limbus in ocular physiology, and the limbal functionality is crucial for corneal health and the entire visual system. Since the anterior limbus containing epithelial structures and limbal epithelial stem cells has been extensively reviewed, this article is focused on the posterior limbus. We have discussed the structural organization and cellular components of the region beneath the limbal epithelium, the characteristics of stem cell types: namely corneal stromal stem cells, endothelial progenitors and trabecular meshwork stem cells, and recent advances leading to the emergence of potential cell therapy options to replenish their respective mature cell types and to correct defects causing corneal abnormalities. We have reviewed different clinical disorders associated with defects of the posterior limbus and summarized the available preclinical and clinical evidence about the developing topic of cell-based therapy for corneal disorders.

Ex vivo ocular perfusion model to study vascular physiology in the mouse eye

Several hypotheses have been tested to understand whole organ regulation in other organs such as the brain and kidney, but no such hypothesis has yet been proposed for ocular circulations. To some extent resolve this deficit our ex vivo mouse eye perfusion model takes the first step in elucidating the mechanisms controlling the individual components of the ocular circulation. Various isolated ocular vascular preparations have been utilized in studies of ocular vascular biology, physiology, and pharmacology, including studies on both normal and pathological conditions. However, there is still significant potential for further studies to improve our understanding of ocular circulation and its regulation. The choroid specifically is inaccessible to direct visualization due to the retina's high metabolic requirement with a transparency that cannot be compromised by an overly rich vascular network on the inner retinal side hindering the visualization of the choroid. In this technical paper, we provide a detailed description of all the steps to be followed from the enucleation of mouse eyes to cannulation of the ophthalmic artery and perfusion and ex vivo confocal microscopy imaging of the dynamic nature of the choroid circulation.

Investigating the effectiveness of Difluprednate-Loaded core-shell lipid-polymeric hybrid nanoparticles for ocular delivery

Uveitis is a sight-threatening disease that causes inflammation in the uvea; difluprednate (DFB) is the first approved drug molecule for postoperative pain, inflammation, and endogenous uveitis. Complex ocular physiology and structure make it difficult to deliver drugs to the eye. Increased permeation and retention in the layer of the eye are required to improve the bioavailability of ocular drugs. In the current research investigation, DFB-loaded lipid polymer hybrid nanoparticles (LPHNPs) were designed and fabricated to enhance the corneal permeation and sustained release of DFB. A well-established two-step approach was used to fabricate the DFB-LPHNPs, comprising of Poly-Lactic-co-Glycolic Acid (PLGA) core that entrapped the DFB and DFB loaded PLGA NPs covered by lipid shell. The manufacturing parameters were optimized for the preparation of DFB-LPHNPs; the optimal DFB-LPHNPs showed a mean particle size of 117.3 ± 2.9 nm, suitable for ocular administration and high entrapment efficiency of 92.45 ± 2.17 % with neutral pH (7.18 ± 0.02) and isotonic Osmolality (301 ± 3 mOsm/kg). Microscopic examination confirms the core–shell morphological structure of DFB-LPHNPs. The prepared DFB-LPHNPs were extensively characterized using spectroscopic techniques and physicochemical characterization, which confirms the entrapment of the drug and the formation of the DFB-LPHNPs. The confocal laser scanning microscopy studies revealed that Rhodamine B-loaded LPHNPs were penetrated into stromal layers of the cornea in ex-vivo conditions. The DFB-LPHNPs showed a sustained release pattern in simulated tear fluid and 4- folds enhanced permeation of DFB as compared to pure DFB solution. The ex-vivo histopathological studies revealed that DFB-LPHNPs didn't cause any damage or no alteration in the cellular structure of the cornea. Additionally, the results of the HET-CAM assay confirmed that the DFB-LPHNPs were not toxic for ophthalmic administration.

Characterization of Porcine Ocular Surface Epithelial Microenvironment.

The porcine ocular surface is used as a model of the human ocular surface; however, a detailed characterization of the porcine ocular surface has not been documented. This is due, in part, to the scarcity of antibodies produced specifically against the porcine ocular surface cell types or structures. We performed a histological and immunohistochemical investigation on frozen and formalin-fixed, paraffin-embedded ocular surface tissue from domestic pigs using a panel of 41 different antibodies related to epithelial progenitor/differentiation phenotypes, extracellular matrix and associated molecules, and various niche cell types. Our observations suggested that the Bowman's layer is not evident in the cornea; the deep invaginations of the limbal epithelium in the limbal zone are analogous to the limbal interpalisade crypts of human limbal tissue; and the presence of goblet cells in the bulbar conjunctiva. Immunohistochemistry analysis revealed that the epithelial progenitor markers cytokeratin (CK)15, CK14, p63α, and P-cadherin were expressed in both the limbal and conjunctival basal epithelium, whereas the basal cells of the limbal and conjunctival epithelium did not stain for CK3, CK12, E-cadherin, and CK13. Antibodies detecting marker proteins related to the extracellular matrix (collagen IV, Tenascin-C), cell-matrix adhesion (β-dystroglycan, integrin α3 and α6), mesenchymal cells (vimentin, CD90, CD44), neurons (neurofilament), immune cells (HLA-ABC; HLA-DR, CD1, CD4, CD14), vasculature (von Willebrand factor), and melanocytes (SRY-homeobox-10, human melanoma black-45, Tyrosinase) on the normal human ocular surface demonstrated similar immunoreactivity on the normal porcine ocular surface. Only a few antibodies (directed against N-cadherin, fibronectin, agrin, laminin α3 and α5, melan-A) appeared unreactive on porcine tissues. Our findings characterize the main immunohistochemical properties of the porcine ocular surface and provide a morphological and immunohistochemical basis useful to research using porcine models. Furthermore, the analyzed porcine ocular structures are similar to those of humans, confirming the potential usefulness of pig eyes to study ocular surface physiology and pathophysiology.

Probing dietary triacylglycerol metabolism and meibogenesis in mice: A stable isotope-labeled tracer liquid chromatography–tandem mass spectrometry study

Exocrine Meibomian glands (MGs) play a central role in the ocular physiology and biochemistry by producing in situ and, mostly, de novo, a secretion (meibum), which is composed of a complex mixture of homologous lipids of various classes, in a metabolic pathway termed meibogenesis. Recent in vivo experiments with a number of mouse models demonstrated that inactivation of any of the major genes of meibogenesis led to alterations in the lipid composition of meibum and severe ocular and MG abnormalities that replicated various human ocular pathologies. However, the role of dietary lipids in meibogenesis, and in the onset and/or alleviation of these diseases, remains controversial. To uncover the role of dietary lipids, the metabolic transformations of a dietary lipid tracer - stable isotope-labeled glyceryl tri(oleate-1,2,3,7,8-13C5) (13C15-TO) - were investigated using LC-high-resolution TOF-MS/MS. We demonstrated that major metabolic transformations of the tracer occurred in the stomach and small intestines where 13C15-TO underwent immediate and extensive transesterification into 13C5- and 13C10-substituted triacylglycerols of various lengths, giving a mixture of 13C-labeled compounds that remain virtually unchanged in the mouse plasma, liver, and white adipose tissue, but were almost undetectable in the feces. Importantly, the tracer and its metabolites were virtually undetectable in MGs, even after 4 weeks of daily supplementation. Notably, unbiased Principal Component Analysis of the data revealed no measurable changes in the overall chemical composition of meibum after the treatment, which implies no direct effect of dietary triacylglycerols on meibogenesis, and left their systemic effects as the most likely mechanism.

Microfluidic contact lenses for ocular diagnostics and drug delivery

AbstractThe human eye and tear provide essential physiological information for the detection of ocular dysfunctions and therapy monitoring. The measurements of biomarkers in tear composition are critical for disease diagnosis and early interventions. Hence, significant efforts are dedicated to the development of functional contact lenses that can quantify tear analytes and ocular physiological condition. The combination of microfluidics and contact lens technologies offer real‐time monitoring of ocular physiology and timely detection of eye disorders through wireless components. This review discusses the fundamentals of microfluidic contact lenses and their diverse applications in ophthalmic diagnostics and drug delivery. It also elucidates the strategies for the commercialization of microfluidic contact lenses to create clinical and point‐of‐care products.

Ocular surface physiology and aqueous tear secretion in cats of diverse cephalic conformations.

To describe normative ocular surface and aqueous tear testing data for cats of various cephalic conformation. Fifty-three healthy adult cats (11 British Shorthair, 11 Burmese, 10 Devon Rex, 10 Scottish Fold, and 11 Sphynx). Blink rate, corneal tactile sensation (CTS), and Schirmer tear test with or without topical anesthesia (STT-1, STT-2) and with nasolacrimal stimulation (NL-STT1, NL-STT2) were assessed. Palpebral fissure length (PFL) and skull morphology were measured, and cephalic index (CI) and craniofacial ratio (CFR) calculated. Mean ± SD test results were as follows: blink rate (5.0± 2.3 blinks/min), CTS (3.2± 0.7cm), STT-1 (11.2± 4.3 mm/min), STT-2 (6.7± 3.6 mm/min), NL-STT1 (13.4± 5.7 mm/min), NL-STT2 (13.5± 5.2 mm/min), and PFL (2.0± 0.2cm). Corneal sensitivity did not differ significantly among breeds (p= .152) but was negatively correlated with body weight (r= -.32, p= .019). STT-1 significantly differed among breeds (p< .001) and was lowest in Sphynx cats (8.7± 4.3 mm/min). A positive correlation was detected between STT-1 values at 30 and 60 s (r= .98; p< .001). The nasolacrimal reflex significantly increased STT in anesthetized and unanesthetized eyes (approximately +100% and +20%, respectively; p≤ .002). STT-1 tended to be higher in intact versus neutered cats (p= .062). Age did not impact any test result (p≥ .085). Normative data described here serve as a baseline for future studies assessing ocular surface disease in multiple feline breeds. Unlike dogs, brachycephalic cats did not have lower CTS or STT-1 than non-brachycephalic cats.