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Investigative Ophthalmology & Visual... Jul 2024Soat1/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...
PURPOSE
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.
METHODS
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.
RESULTS
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).
CONCLUSIONS
These findings suggest a direct involvement of Soat1/SOAT1 in MGs in maintaining ocular surface homeostasis, in general, and corneal health, specifically.
Topics: Animals; Mice; Homeostasis; Meibomian Glands; Tears; Mice, Knockout; Cornea; Mice, Inbred C57BL; Lipid Metabolism
PubMed: 38953847
DOI: 10.1167/iovs.65.8.2 -
Investigative Ophthalmology & Visual... Jul 2024The purpose of this study was to investigate the role and mechanism of microtubule-associated protein light chain-3 (LC3)-associated phagocytosis (LAP) in the immune...
PURPOSE
The purpose of this study was to investigate the role and mechanism of microtubule-associated protein light chain-3 (LC3)-associated phagocytosis (LAP) in the immune response to Aspergillus fumigatus (A. fumigatus) keratitis.
METHODS
The formation of single-membrane phagosomes was visualized in the corneas of healthy or A. fumigatus-infected humans and C57BL/6 mice using transmission electron microscopy (TEM). Rubicon siRNA (si-Rubicon) was used to block Rubicon expression. RAW 264.7 cells or mice corneas were infected with A. fumigatus with or without pretreatment of si-Rubicon and scrambled siRNA. RAW 264.7 cells were pretreated with Dectin-1 antibody or Dectin-1 overexpressed plasmid and then stimulated with A. fumigatus. Flow cytometry was used to label macrophages in normal and infected corneas of mice. In mice with A. fumigatus keratitis, the severity of the disease was assessed using clinical scores. We used lentiviral technology to transfer GV348-Ubi-GFP-LC3-II-SV40-Puro Lentivirus into the mouse cornea. The GFP-LC3 fusion protein was visualized in corneal slices using a fluorescence microscope. We detected the mRNA and protein expressions of the inflammatory factors IL-6, IL-1β, and IL-10 using real-time PCR (RT-PCR) and ELISA. We detected the expression of LAP-related proteins Rubicon, ATG-7, Beclin-1, and LC3-II using Western blot or immunofluorescence.
RESULTS
Accumulation of single-membrane phagosomes within macrophages was observed in the corneas of patients and mice with A. fumigatus keratitis using TEM. Flow cytometry (FCM) analysis results show that the number of macrophages in the cornea of mice significantly increases after infection with A. fumigatus. LAP-related proteins were significantly elevated in the corneas of mice and RAW 264.7 cells after infection with A. fumigatus. The si-Rubicon treatment elevated the clinical score of mice. In A. fumigatus keratitis mice, the si-Rubicon treated group showed significantly higher expression of IL-6 and IL-1β and lower expression of IL-10 and LC3-II compared to the control group. In RAW 264.7 cells, treatment with the Dectin-1 overexpressed plasmid upregulated the expression of LAP-related proteins, a process that was significantly inhibited by the Dectin-1 antibody.
CONCLUSIONS
LAP participates in the anti-inflammatory immune process of fungal keratitis (FK) and exerts an anti-inflammatory effect. LAP is regulated through the Dectin-1 signaling pathway in A. fumigatus keratitis.
Topics: Animals; Aspergillus fumigatus; Mice; Mice, Inbred C57BL; Aspergillosis; Phagocytosis; Humans; Microtubule-Associated Proteins; Keratitis; Eye Infections, Fungal; Disease Models, Animal; Macrophages; Female; Flow Cytometry; Microscopy, Electron, Transmission; Male; Cornea
PubMed: 38953845
DOI: 10.1167/iovs.65.8.4 -
Acta Ophthalmologica Jul 2024To characterise the retinal vasculometry of a Danish eye and vision cohort and examine associations with systolic blood pressure (BP), diastolic BP, mean arterial BP,...
Longitudinal associations of retinal vessel morphology with intraocular pressure and blood pressure at follow-up visit-Findings from a Danish eye and vision cohort, Project FOREVER.
PURPOSE
To characterise the retinal vasculometry of a Danish eye and vision cohort and examine associations with systolic blood pressure (BP), diastolic BP, mean arterial BP, and intraocular pressure (IOP).
DESIGN
Longitudinal study.
METHODS
The retinal vasculature of fundus images from the FOREVER (Finding Ophthalmic Risks and Evaluating the Value of Eye exams and their predictive Reliability) cohort was analysed using a fully automated image analysis program. Longitudinal associations of retinal vessel morphology at follow-up visit with IOP (baseline and follow-up) and BP (follow-up) were examined using multilevel linear regression models adjusting for age, sex and retinal vasculometry at baseline as fixed effects and person as random effect. Width measurements were additionally adjusted for the spherical equivalent.
RESULTS
A total of 2089 subjects (62% female) with a mean age of 61 (standard deviation 8) years and a mean follow-up period of 4.1 years (SD 0.6 years) were included. The mean arteriolar diameter was approximately 20% thinner than the mean venular diameter, and venules were about 21%-23% less tortuous than arterioles. BP at follow-up was associated with decreased arteriolar diameter from baseline to follow-up. After adjusting for baseline IOP, IOP at follow-up was associated with increased arteriolar tortuosity above baseline (0.59%, 95% CI 0.08-1.10, p-value 0.024).
CONCLUSION
In a Danish eye and vision cohort, variations in BP and alterations in IOP over time were associated with changes in the width and tortuosity of retinal vessels. Our findings contribute novel insights into retinal vascular alterations over time.
PubMed: 38953839
DOI: 10.1111/aos.16737 -
Indian Journal of Public Health Apr 2024The WHO's World Health Day 2024 slogan, "My health, my right," has been unpacked through the lens of an evolving social epidemiological understanding. The operative part...
The WHO's World Health Day 2024 slogan, "My health, my right," has been unpacked through the lens of an evolving social epidemiological understanding. The operative part of the theme merely reiterates international positions that have been established for a long and is unable to adequately incorporate advances in the understanding of the central role that structural determinants play in the production of ill-health. Given the urgency of addressing Sustainable Development Goal and Universal Health Coverage goals, the reduction of health inequities through the promotion of social justice is as much a governance imperative as moral.
Topics: Humans; Social Justice; Global Health; Social Determinants of Health; Right to Health; World Health Organization; Health Inequities; Sustainable Development; Universal Health Insurance
PubMed: 38953828
DOI: 10.4103/ijph.ijph_478_24 -
Chaos (Woodbury, N.Y.) Jul 2024Reservoir computing (RC) is a machine learning paradigm that excels at dynamical systems analysis. Photonic RCs, which perform implicit computation through optical...
Reservoir computing (RC) is a machine learning paradigm that excels at dynamical systems analysis. Photonic RCs, which perform implicit computation through optical interactions, have attracted increasing attention due to their potential for low latency predictions. However, most existing photonic RCs rely on a nonlinear physical cavity to implement system memory, limiting control over the memory structure and requiring long warm-up times to eliminate transients. In this work, we resolve these issues by demonstrating a photonic next-generation reservoir computer (NG-RC) using a fiber optic platform. Our photonic NG-RC eliminates the need for a cavity by generating feature vectors directly from nonlinear combinations of the input data with varying delays. Our approach uses Rayleigh backscattering to produce output feature vectors by an unconventional nonlinearity resulting from coherent, interferometric mixing followed by a quadratic readout. Performing linear optimization on these feature vectors, our photonic NG-RC demonstrates state-of-the-art performance for the observer (cross-prediction) task applied to the Rössler, Lorenz, and Kuramoto-Sivashinsky systems. In contrast to digital NG-RC implementations, we show that it is possible to scale to high-dimensional systems while maintaining low latency and low power consumption.
PubMed: 38953754
DOI: 10.1063/5.0212158 -
The Review of Scientific Instruments Jul 2024We describe a setup for time- and angle-resolved photoemission spectroscopy with wavelength-tunable excitation and an extreme ultraviolet probe. It is enabled by using...
We describe a setup for time- and angle-resolved photoemission spectroscopy with wavelength-tunable excitation and an extreme ultraviolet probe. It is enabled by using the 10 kHz twin Ti:sapphire amplifiers seeded by the common Ti:sapphire oscillator. The typical probe energy is 21.7 eV, and the wavelength of the pump excitation is tuned between 2400 and 1200 nm by using the optical parametric amplifier. The spectral width of the extreme ultraviolet probe is 53 meV, and the time resolution is dependent on the wavelength for the pump, better than 60 fs for the pump energy >0.7 eV. This system enables the pump energy to be matched with a specific interband transition and to probe a wider energy-momentum space. We present the results for the prototypical materials of highly oriented pyrolytic graphite and Bi2Se3 to show the performance of our system.
PubMed: 38953720
DOI: 10.1063/5.0204133 -
Ophthalmic Genetics Jul 2024Bardet-Biedl Syndrome (BBS) is a rare autosomal recessive ciliopathy. Within corneal development, primary cilia serve a critical role. We sought to investigate the...
PURPOSE
Bardet-Biedl Syndrome (BBS) is a rare autosomal recessive ciliopathy. Within corneal development, primary cilia serve a critical role. We sought to investigate the association of BBS with corneal astigmatism among a cohort of patients with BBS.
METHODS
This was a cross-sectional, retrospective study performed at a pediatric ophthalmology department of a tertiary hospital. The study enrolled 45 patients with genetically confirmed Bardet-Biedl syndrome, encompassing a total of 90 eyes observed from February 2011 to August 2021. Spherical and cylindrical refractive errors and keratometry outcome measures, including diopter (D) values at the flattest and steepest axes, were recorded. Corneal astigmatism of greater than 3D is considered extreme corneal astigmatism based on previously published data.
RESULTS
Among 45 patients (M:26; F:19), the mean age was 16.4 ± 8.2 years, and the mean best-corrected visual acuity was 20/60. The most common molecular diagnosis was , seen in 24 of 45 (53.3%). Among all the patients, the mean spherical refractive error was -2.9 ± 3.8D. The mean cylindrical refractive error was 2.6 ± 1.5D. The mean keratometry values at the flattest axis was 43.5 ± 5.3D (39.4-75.0) and at the steepest axis was 47.2 ± 7.3D(41.5-84.0). Among all the patients with BBS, the mean corneal astigmatism was 3.7 ± 1.0D(0.5-7.1), which is considered extreme.
CONCLUSION
A cohort of individuals with BBS demonstrated high corneal astigmatism. These results suggest an association between corneal astigmatism and primary ciliary dysfunction and may assist in clinical management and future therapeutic targets among BBS and other corneal disorders.
PubMed: 38953718
DOI: 10.1080/13816810.2024.2357296 -
Chemical Communications (Cambridge,... Jul 2024The emergence of materials that can effectively convert photon energy (light) into motion (mechanical work) and change their shapes on command is of great interest for... (Review)
Review
The emergence of materials that can effectively convert photon energy (light) into motion (mechanical work) and change their shapes on command is of great interest for their potential in the fabrication of devices (powered by light) that will revolutionize the technologies of optical actuators, smart medical devices, soft robotics, artificial muscles and flexible electronics. Recently, metal-organic crystals have emerged as desirable smart hybrid materials that can hop, split and jump. Thus, their incorporation into polymer host objects can control movement from molecules to millimetres, opening up a new world of light-switching smart materials. This feature article briefly summarizes the recent part of the fast-growing literature on photomechanical properties in metal-organic crystals, such as coordination compounds, coordination polymers (CPs), and metal-organic frameworks (MOFs). The article highlights the contributions of our group along with others in this area and aims to provide a consolidated idea of the engineering strategies and structure-property relationships of these hybrid materials for such rare phenomena with diverse potential applications.
PubMed: 38953709
DOI: 10.1039/d4cc02655a -
Materials Horizons Jul 2024Anisotropy in mechanical, optical and thermal sensors in a spatial direction has many applications in health care, robotics, aerospace, and tissue engineering. In...
Anisotropy in mechanical, optical and thermal sensors in a spatial direction has many applications in health care, robotics, aerospace, and tissue engineering. In particular, wearable and implantable sensors respond to stretching and bending strains that probe mechanical energy and track physiological signals. Hence, the development of anisotropic pressure sensors with true piezoelectric (PE) signals is of utmost importance to achieve efficient devices. Herein, a simple and efficient method is developed for high longitudinal and transverse responses, with an approach to isolating a true piezoelectric signal. The electrospun (ES) polarity of oriented dipoles inside flexible fibers gives rise to a high longitudinal/transverse PE response of both lateral and transverse strains. Nanofibers of poly(vinylidene-chlorotrifluoroethylene) copolymers contain poled dipoles, up to 86%, that promote an enhanced PE coefficient of 42 pm V in the case of negative polarity-based electrospinning. It is 40% higher in composition than the commonly adopted positive polarity-biased electrospinning process. We demonstrated the advantage of such a high PE coefficient by the enhanced sensitivity of the longitudinal (Ls = 0.3 V kPa, Ls = 0.07 μA kPa) as well as transverse (Ts = 1.0 V kPa, Ts = 0.8 μA kPa) PE response. To counter the ambiguity of high transverse response as compared to longitudinal in electrospun fiber-based devices, a facile method is proposed to isolate the ferroelectret, triboelectric and piezoelectric signals in a fiber-based hybrid device with their independent charge generation mechanisms.
PubMed: 38953680
DOI: 10.1039/d4mh00540f -
Expert Opinion on Biological Therapy Jul 2024Neovascular age-related macular degeneration (nAMD) represents a leading cause of severe visual impairment in individuals over 50 years of age in developed nations.... (Review)
Review
INTRODUCTION
Neovascular age-related macular degeneration (nAMD) represents a leading cause of severe visual impairment in individuals over 50 years of age in developed nations. Intravitreal anti-vascular endothelial growth factor (VEGF) injections have become the standard of care for treating nAMD; however, monthly or bimonthly dosing represents significant time and cost burden due to the disease's chronic nature and limited medication half-life.
AREAS COVERED
This review summarizes innovative therapeutics and delivery methods for nAMD. Emerging methods for extended drug delivery include high molar concentration anti-VEGF drugs, intravitreal sustained release devices, reservoirs for intravitreal delivery, and gene therapy biofactories. In addition to VEGF-A, therapies targeting inhibition of VEGF-C and D, the angiopoetin-2 (Ang-2)/Tie-2 pathway, tyrosine kinases, and integrins are reviewed.
EXPERT OPINION
The evolving therapeutic landscape of nAMD is rapidly expanding our toolkit for effective and durable treatment. Recent FDA approvals of faricimab (Vabysmo) and high dose aflibercept (Eylea HD) for nAMD with potential extension of injection intervals up to four months have been promising developments for patients and providers alike. Further research and innovation, including novel delivery techniques and pharmacologic targets, is necessary to validate the efficacy of developing therapeutics and characterize real-world outcomes. demonstrating promise in expanding treatment durability.
PubMed: 38953649
DOI: 10.1080/14712598.2024.2374869