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1.
Int Ophthalmol ; 43(12): 4803-4814, 2023 Dec.
Article En | MEDLINE | ID: mdl-37851140

PURPOSE: To evaluate the relationship between the nonperfusion area (NPA) from widefield optical coherence tomography angiography (OCTA) and macular vascular parameters in diabetic retinopathy (DR). METHODS: In total, 51 eyes from 51 patients with proliferative DR (PDR) or moderate/severe non-PDR were included. Widefield OCTA using the Zeiss Plex Elite 9000 was performed. A semi-automatic algorithm calculated the percentages of the NPA within the total image. Macular OCTA (3 × 3 mm and 6 × 6 mm area) was scanned using the RTVue-XR Avanti. Vessel density (VD) was automatically separated into the superficial (SCP) and deep capillary plexus (DCP), and foveal avascular zone (FAZ) measurements were computed according to the parafoveal (1-3 mm) and perifoveal (3-6 mm) regions. RESULTS: A negative correlation was found between the average VD of the SCP and DCP obtained 3 × 3 mm and 6 × 6 mm area and the NPA. Multiple regression analysis revealed that the temporal-perifoveal region most negatively correlated with the NPA (r = - 0.55, p < 0.0001). No correlation was found between FAZ measurements and DR severity (area, p = 0.07; perimeter, p = 0.13). CONCLUSION: Diabetic macular nonperfusion was significantly associated with the NPA from widefield OCTA. In particular, the temporal-perifoveal DCP disorder may be a sensitive indicator of wide NPA.


Diabetes Mellitus , Diabetic Retinopathy , Macula Lutea , Humans , Diabetic Retinopathy/diagnosis , Retinal Vessels , Fluorescein Angiography/methods , Tomography, Optical Coherence/methods , Macula Lutea/blood supply
2.
Exp Eye Res ; 234: 109571, 2023 09.
Article En | MEDLINE | ID: mdl-37468028

Blinking is regarded as mechanical stimulation of fluid shear stress on the corneal epithelial cells. Therefore, we evaluated whether fluid shear stress affects matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in cultured human corneal epithelial cells (HCECs). No other study has shown the influence of fluid shear stress on HCECs regarding mRNA expression and the protein levels of MMPs. Cultured HCECs were exposed to shear stress (0, 1.2, 12 dyne/cm2) for 12 and 24 h with the parallel-plate type of flow chamber. Gene expression of MMPs and TIMPs was measured by real-time polymerase reaction. Concentrations of MMP-1 and MMP-9 in cell lysates were determined using bead-based amplified luminescent proximity homogenous assay-linked immunosorbent assay. The expression of MMP-9 and MMP-1 in HCECs exposed to low and high flow for 12 and 24 h, respectively, increased significantly compared with those under static conditions. The expression of MMP-9 in the cells exposed to high flow for 24 h increased significantly compared with those under static and low flow conditions. Levels of MMP-9 in cell lysates exposed to fluid flow for 24 h were elevated significantly with increasing shear stress. Fluid shear stress exerted on HCECs affected MMPs, which was associated with inflammation and pathogenesis. Mechanical stress induced by blinking might influence expression of MMPs on the ocular surface. Further studies are warranted to establish the molecular mechanism of shear stress-induced alternations of MMPs.


Matrix Metalloproteinase 1 , Matrix Metalloproteinase 9 , Humans , Cells, Cultured , Cornea/metabolism , Epithelial Cells/metabolism , Matrix Metalloproteinase 1/genetics , Matrix Metalloproteinase 1/metabolism , Matrix Metalloproteinase 9/genetics , Stress, Mechanical
3.
Molecules ; 28(3)2023 Jan 30.
Article En | MEDLINE | ID: mdl-36770976

Thermal energy storage (TES) is vital to the absorption and release of plenty of external heat for various applications. For such storage, phase change material (PCM) has been considered as a sustainable energy material that can be integrated into a power generator. However, pure PCM has a leakage problem during the phase transition process, and we should fabricate a form stable PCM composite using some supporting materials. To prevent the leakage problem during the phase transition process, two different methods, microencapsulation and 3D porous infiltration, were used to fabricate PCM composites in this work. It was found that both microsphere and 3D porous aerogel supported PCM composites maintained their initial solid state without any leakage during the melting process. Compared with the microencapsulated PCM composite, the 3D porous aerogel supported PCM exhibited a relatively high weight fraction of working material due to its high porosity. In addition, the cross-linked graphene aerogel (GCA) could reduce volume shrinkage effectively during the infiltration process, and the GCA supported PCM composite kept a high latent heat (∆H) and form stability.

4.
Retina ; 43(2): 303-312, 2023 02 01.
Article En | MEDLINE | ID: mdl-36695800

PURPOSE: To report the pattern and characteristics of drusen subtypes in Asian populations and the association with choroidal thickness. METHODS: This is the cross-sectional analysis of the population-based cohort study. Two thousand three hundred and fifty-three eyes of 1,336 Chinese and Indian participants aged older than 50 years, eyes with best-corrected visual acuity better than 20/60, and without other retinal diseases were recruited. Pachydrusen, reticular pseudodrusen, soft and hard drusen were graded on both color fundus photographs, and optical coherence tomography imaging with automated segmentation yielding and measurements of choroidal thickness. RESULTS: Nine hundred and fifty-five Chinese and 381 Indians were included in the final analysis. The pattern of pachydrusen, soft drusen, hard drusen, and reticular pseudodrusen was 14.0%, 3.7%, 12.5%, and 0.2%, respectively. Mean choroidal thickness was the thickest in eyes with pachydrusen (298.3 µm; 95% confidence interval: 290.5-306.1), then eyes with hard (298.1 µm; 95% confidence interval: 290.6-305.5) and soft drusen (293.7 µm; 95% confidence interval: 281.9-305.4) and thinnest in eyes without drusen (284.6 µm; 95% confidence interval: 280.5-288.7). Systemic associations of the various drusen subtypes also differed. CONCLUSION: Patterns, characterization and choroidal thickness of drusen subtypes, and their associations provide insights into the Asian phenotypic spectrum of age-related macular degeneration and the underlying pathogenesis.


East Asian People , Retinal Drusen , Humans , Aged , Cohort Studies , Cross-Sectional Studies , Singapore/epidemiology , Retrospective Studies , Retinal Drusen/diagnosis , Retinal Drusen/epidemiology , Retinal Drusen/etiology , Tomography, Optical Coherence/methods , Fluorescein Angiography
5.
Transl Vis Sci Technol ; 11(10): 11, 2022 10 03.
Article En | MEDLINE | ID: mdl-36201201

Purpose: The purpose of this study was to evaluate the diagnostic performance of retinal blood flow (RBF) measured with the Doppler optical coherence tomography (OCT) segmental scanning method to distinguish between healthy and glaucoma eyes. Methods: Fifty-eight patients with normal tension glaucoma (NTG) who had a single-hemifield visual field defect and 44 age-matched healthy subjects were enrolled. Retinal nerve fiber layer thickness (RNFLT) was measured with swept-source OCT. Superior and inferior temporal arteries (TAs) and temporal veins (TVs) RBF were measured with Doppler OCT. The area under the curve (AUC) of the receiver operating characteristic (ROC) was used to compare the diagnostic performances in the damaged and normal hemispheres. Results: Multivariate regression analysis showed TA RBF and TV RBF were significantly reduced in the damaged and normal hemispheres. The ROC analysis showed that the AUC for quadrant RNFLT, TA RBF, and TV RBF were 0.973, 0.909, and 0.872 in the damaged hemisphere, respectively. The AUC values in the normal hemisphere were 0.783, 0.744, and 0.697, respectively. The combination of quadrant RNFLT and TA/TV RBF had a greater AUC than quadrant RNFLT alone in both damaged (AUC = 0.987) and normal (AUC = 0.825) hemispheres. Conclusions: In NTG eyes with single-hemifield damage, the RBF was found to be significantly reduced in the damaged and normal hemispheres independent from structural changes. The combination of RNFLT and RBF could improve diagnostic performances for glaucoma. Translational Relevance: Combining morphological and blood flow measurements with Doppler OCT may be useful in glaucoma diagnosis.


Glaucoma , Low Tension Glaucoma , Glaucoma/diagnostic imaging , Humans , Low Tension Glaucoma/diagnostic imaging , Nerve Fibers , Retina , Retinal Ganglion Cells , Tomography, Optical Coherence/methods
6.
Pharmaceuticals (Basel) ; 15(4)2022 Apr 15.
Article En | MEDLINE | ID: mdl-35455480

This paper evaluates a one-year treatment outcome after full or reduced photodynamic therapy (PDT) and anti-vascular endothelial growth factor (VEGF) combination therapy for pachychoroid neovasculopathy (PNV). After the initial combination therapy, a total of 29 eyes from 29 patients (16 for full treatment and 13 for reduced treatment), exhibited reduced, central retinal thickness and central choroidal thickness, and the improvements were maintained for 1 year after the initial combination therapy. Twenty-two eyes (75.9%) required no additional treatments for 1 year. The recurrence rate was 31.3% in the full treatment and 15.4% in the reduced treatment, with no significant differences between them. One shot of anti-VEGF and full or reduced PDT combination therapy had similar efficacy in treating PNV. Further prospective, large-scale, and long-term studies are required to determine a better treatment for PNV.

8.
Int J Ophthalmol ; 15(3): 388-393, 2022.
Article En | MEDLINE | ID: mdl-35310043

AIM: To investigate changes in extracellular matrix (ECM) gene expression in human trabecular meshwork (HTM) cells in response to mechanical fluid flow stimulation. METHODS: HTM cells were grown on a glass plate coated with 0.02% type I collagen (COL) and exposed to shear stress (0, 0.2, 1.0 dyne/cm2) for 12h. Changes in genes related to the ECM were evaluated by real-time reverse transcriptase-polymerase chain reaction. Phosphorylation of Smad2 protein was investigated by Western blotting. RESULTS: After mechanical stimulation, COL type 4 alpha 2, COL type 6 alpha 1, and fibronectin-1 mRNA were significantly higher than the static control (P<0.05, <0.05, and <0.01, respectively). The metalloproteinase-2 and plasminogen activator inhibitor-1 mRNA were significantly higher than the static control (P<0.05 and <0.01, respectively), while the differences in the tissue inhibitors of metalloproteinases-2 mRNA were not significant. The phosphorylation of Smad2 levels was significantly higher compared to the static control cells. CONCLUSION: Changes in the expressions of genes associated ECM metabolism result in HTM cells after mechanical stimulation. The mechanical stimulation of the aqueous humor to the trabecular meshwork may promote ECM turnover and contribute to intraocular pressure homeostasis.

9.
Pharmaceuticals (Basel) ; 14(11)2021 Nov 10.
Article En | MEDLINE | ID: mdl-34832922

To evaluate choroidal volume and thickness changes after photodynamic therapy (PDT) for chronic central serous chorioretinopathy (CSC). Chronic CSC eyes with a history of PDT were selected. Average choroidal volume, average choroidal thickness, the maximum and minimum choroidal thickness of the macula irradiated area and peripheral non-irradiated areas before and after one and three months of treatment were examined. A total of 14 patients with chronic CSC and 9 controls without any eye pathology were enrolled. The mean choroidal volume in CSC before and, and after one and three months of treatment were 2.36 (standard deviation: 0.70), 1.90 (0.69), 1.86 (0.66) mm3 for the central area, 1.25 (0.38), 1.14 (0.35), 1.13 (0.34) mm3 for superior nasal area, 1.47 (0.41), 1.28 (0.43), 1.26 (0.43) mm3 for superior temporal area, 1.07 (0.49), 0.95 (0.38), 0.93 (0.35) mm3 for inferior nasal area, 1.17 (0.38), 1.04 (0.32), 1.03 (0.33) mm3 for inferior temporal area. This study revealed the choroidal volume changes in a short period after PDT and a decrease in unirradiated choroidal volume was also shown after the treatment. The algorithm provided on the ARI Network enables to evaluate the choroidal changes quantitatively and qualitatively.

10.
Transl Vis Sci Technol ; 10(13): 25, 2021 11 01.
Article En | MEDLINE | ID: mdl-34792557

Purpose: We aimed to explore the velocity waveform characteristics of the retinal artery associated with age and the cardio-ankle vascular index (CAVI) as a conventional arterial stiffness marker by applying the Doppler optical coherence tomography (DOCT) flowmeter. Methods: In this cross-sectional study, DOCT flowmeter imaging was performed in 66 participants aged 21 to 83 years (17 men, 49 women) with no history of eye diseases and no systemic diseases, except for hypertension. Retinal blood velocity waveform was analyzed where several parameters in time (upstroke time, T1, T2, T3, and T4) and area under the waveform (area elevation, area declination, A1, A2, A3, and A4) were extracted. Systolic blood pressure-adjusted Pearson's coefficients were calculated to determine the correlations of each parameter with age or CAVI. Results: Corrected upstroke time (UTc) was the waveform parameter most positively correlated with age (r = 0.497, P < 0.001). Area declination was the waveform parameter most negatively correlated with age (r = -0.682, P < 0.001) and CAVI (r = -0.601, P < 0.001). Conclusions: We extracted the waveform parameters associated with the risks of arterial stiffening. The velocity waveform analysis of the retinal artery with DOCT flowmeter potentially could become a new method for arterial stiffness identification. Translational Relevance: DOCT flowmeter could evaluate arterial stiffening in a different way from the conventional method of measuring arterial stiffening using pressure waveform. Because the DOCT flowmeter can easily, quickly, and noninvasively provide a retinal blood velocity waveform, this system could be useful as a routine medical examination for arterial stiffening.


Cardio Ankle Vascular Index , Hypertension , Aging , Blood Pressure , Cross-Sectional Studies , Female , Humans , Male
11.
J Clin Med ; 10(18)2021 Sep 17.
Article En | MEDLINE | ID: mdl-34575338

This study aimed to investigate the influence of educational pressure on myopia. A less-intense school curriculum was introduced nationally in Japan beginning in 2012 based on a pressure-free education policy. In this retrospective observational study, a total of 1025 Japanese medical students of Asahikawa Medical University underwent measurements of the cycloplegic refractive error and axial length (AL), from 2011 to 2020. The spherical equivalent (SE) and AL were correlated significantly with the fiscal year of births (p = 0.004 and p = 0.034, respectively) only during enforcement of the system of high-pressure education. The SE and AL regression rates during the two educational approaches differed significantly (p = 0.004 and p = 0.037, respectively). The prevalence of high myopia was correlated significantly (p < 0.001) only during the system of high-pressure education. The regression of the prevalence rate of high myopia during the two education approaches differed significantly (p = 0.010). The progression rates of myopia and increased prevalence of high myopia were observed only during high-pressure education, suggesting that not only ophthalmologists but also educators and the government should work on together to control the progression of myopia.

12.
Front Immunol ; 12: 704526, 2021.
Article En | MEDLINE | ID: mdl-34497607

Objective: Baricitinib, a selective inhibitor for janus kinase (JAK) 1 and JAK2, is approved for use in rheumatoid arthritis. Systemic lupus erythematosus (SLE) is recently regarded as a potential candidate targeted by JAK inhibitors because of the relationship between its pathogenesis and JAK/signal transducer and activator of transcription (STAT) pathway-mediated cytokines such as type I interferons. The objective of this study was to determine whether baricitinib could effectively ameliorate SLE using a murine model. Methods: To investigate effects of baricitinib on various autoimmune features, especially renal involvements in SLE, eight-week-old MRL/Mp-Faslpr (MRL/lpr) mice were used as a lupus-prone animal model and treated with baricitinib for eight weeks. Immortalized podocytes and primary podocytes and B cells isolated from C57BL/6 mice were used to determine the in vitro efficacy of baricitinib. Results: Baricitinib remarkably suppressed lupus-like phenotypes of MRL/lpr mice, such as splenomegaly, lymphadenopathy, proteinuria, and systemic autoimmunity including circulating autoantibodies and pro-inflammatory cytokines. It also modulated immune cell populations and effectively ameliorated renal inflammation, leading to the recovery of the expression of structural proteins in podocytes. According to in vitro experiments, baricitinib treatment could mitigate B cell differentiation and restore disrupted cytoskeletal structures of podocytes under inflammatory stimulation by blocking the JAK/STAT pathway. Conclusions: The present study demonstrated that baricitinib could effectively attenuate autoimmune features including renal inflammation of lupus-prone mice by suppressing aberrant B cell activation and podocyte abnormalities. Thus, baricitinib as a selective JAK inhibitor could be a promising therapeutic candidate in the treatment of SLE.


Azetidines/pharmacology , Lupus Erythematosus, Systemic , Podocytes , Purines/pharmacology , Pyrazoles/pharmacology , Sulfonamides/pharmacology , Animals , Disease Models, Animal , Female , Janus Kinase 1/antagonists & inhibitors , Janus Kinase 1/immunology , Janus Kinase 2/antagonists & inhibitors , Janus Kinase 2/immunology , Lupus Erythematosus, Systemic/drug therapy , Lupus Erythematosus, Systemic/immunology , Lupus Erythematosus, Systemic/pathology , Mice , Mice, Inbred MRL lpr , Podocytes/immunology , Podocytes/pathology , Signal Transduction/drug effects
13.
PLoS One ; 16(7): e0254980, 2021.
Article En | MEDLINE | ID: mdl-34283877

This study aimed to evaluate whether long-term insulin treatment is associated with abnormalities in retinal circulation in type 2 diabetic patients. We evaluated 19 eyes of nondiabetic individuals and 68 eyes of type 2 diabetic patients. The eyes of diabetic patients were classified into two groups according to the presence or absence of long-term insulin therapy. We used a Doppler optical coherence tomography flowmeter to measure diameter, velocity, and blood flow in the major temporal retinal artery. The pulsatility ratio (PR) and resistance index (RI), indices of vascular rigidity, were calculated from the blood velocity profile. PR and RI were significantly elevated in type 2 diabetic patients compared with nondiabetic subjects (P < 0.05). In type 2 diabetes patients, PR and RI were significantly higher in patients receiving long-term insulin treatment than in those without (P < 0.01). There was a significant difference in velocity (P < 0.05), but not diameter and blood flow, between nondiabetic subjects and type 2 diabetes patients. No significant difference in diameter, velocity, or blood flow was observed between the groups with and without long-term insulin treatment. Long-term insulin treatment can affect PR and RI, which might be associated with vascular rigidity of the retinal artery in patients with type 2 diabetes.


Diabetes Mellitus, Type 2/metabolism , Insulin/metabolism , Retinal Artery/drug effects , Adult , Aged , Blood Circulation/physiology , Blood Flow Velocity/drug effects , Blood Glucose , Diabetes Mellitus, Type 2/drug therapy , Eye/physiopathology , Female , Hemodynamics/drug effects , Humans , Insulin/therapeutic use , Male , Middle Aged , Regional Blood Flow/drug effects , Retinal Artery/metabolism , Tomography, Optical Coherence/methods , Vascular Resistance/drug effects , Vascular Resistance/physiology
14.
Materials (Basel) ; 14(10)2021 May 20.
Article En | MEDLINE | ID: mdl-34065550

Cu nanofoams are promising materials for a variety of applications, including anodes in high-performance lithium-ion batteries. The high specific surface area of these materials supports a high capacity and porous structure that helps accommodate volume expansion which occurs as batteries are charged. One of the most efficient methods to produce Cu nanofoams is the dealloying of Cu alloy precursors. This process often yields nanofoams that have low strength, thus requiring additional heat treatment to improve the mechanical properties of Cu foams. This paper provides the effects of heat treatment on the microstructures, mechanical properties, and electrochemical performance of Cu nanofoams. Annealing was conducted under both inert and oxidizing atmospheres. These studies ultimately reveal the underlying mechanisms of ligament coarsening during heat treatment.

15.
Molecules ; 26(9)2021 Apr 26.
Article En | MEDLINE | ID: mdl-33925934

Liquid crystal polymer (LCP) composites filled with sepiolite and glass microcapsules were prepared by melt compounding. The composites were extruded using a twin-screw extruder and injection-molded. The objective of this study is to check a possibility of producing a polymeric composite with a low dielectric constant. Physical characteristics of the composites, such as morphological, rheological, mechanical, and electrical properties were analyzed. In particular, the glass microcapsule-reinforced LCP composites showed a significant improvement in lowering the dielectric constant due to its high air content. Additionally, sepiolite could act as an effective filler to improve the mechanical properties of the composites.

16.
Mol Ecol ; 30(6): 1516-1530, 2021 03.
Article En | MEDLINE | ID: mdl-33522041

How underlying mechanisms bias evolution toward predictable outcomes remains an area of active debate. In this study, we leveraged phenotypic plasticity and parallel adaptation across independent lineages of Trinidadian guppies (Poecilia reticulata) to assess the predictability of gene expression evolution during parallel adaptation. Trinidadian guppies have repeatedly and independently adapted to high- and low-predation environments in the wild. We combined this natural experiment with a laboratory breeding design to attribute transcriptional variation to the genetic influences of population of origin and developmental plasticity in response to rearing with or without predators. We observed substantial gene expression plasticity, as well as the evolution of expression plasticity itself, across populations. Genes exhibiting expression plasticity within populations were more likely to also differ in expression between populations, with the direction of population differences more likely to be opposite those of plasticity. While we found more overlap than expected by chance in genes differentially expressed between high- and low-predation populations from distinct evolutionary lineages, the majority of differentially expressed genes were not shared between lineages. Our data suggest alternative transcriptional configurations associated with shared phenotypes, highlighting a role for transcriptional flexibility in the parallel phenotypic evolution of a species known for rapid adaptation.


Biological Evolution , Poecilia , Adaptation, Physiological/genetics , Animals , Phenotype , Poecilia/genetics , Predatory Behavior
17.
Jpn J Ophthalmol ; 65(3): 315-325, 2021 May.
Article En | MEDLINE | ID: mdl-33586090

PURPOSE: Atropine eye drops prevent the progression of myopia, but their use has not been tested in the Japanese schoolchildren population. Here, we evaluate the efficacy and safety of 0.01% atropine eye drops for myopia control in Japanese children. STUDY DESIGN: Multicenter (7 university hospitals), randomized, double-masked, placebo-controlled trial. METHODS: Participants were 171 Japanese schoolchildren aged 6 to 12 years, with progressive myopia, spherical equivalence (SE) of -1.00 to -6.00 diopters (D), and astigmatism of ≤1.5 D. They were randomized to receive either 0.01% atropine (n=85) or placebo (n=86) eye drops once nightly OU for 24 months. Primary and secondary efficacy endpoints were changes in SE and axial length (AL), respectively, from baseline to month 24. RESULTS: Data from 168 subjects were analyzed. At month 24, compliance was similar in both groups (atropine: 83.3%; placebo: 85.7%). The least squares mean change in SE and AL from baseline were, respectively, -1.26 D (95% confidence interval [CI]: -1.35, -1.17) and 0.63 mm (0.59, 0.67) for atropine and -1.48 D (- 1.57, -1.39) and 0.77 mm (0.73, 0.81) for placebo. Inter-group differences were 0.22 D (95% CI: 0.09, 0.35; P < 0.001) for SE and - 0.14 mm (-0.20, -0.08; P < 0.001) for AL. Three patients experienced mild allergic conjunctivitis side effects, with no inter-group difference in incidence (atropine: 2.4%; 2/84 patients; placebo: 1.4%; 1/84 patients). CONCLUSION: With good compliance, 0.01% atropine is effective and safe for preventing the progression of childhood myopia.


Atropine , Myopia, Degenerative , Accommodation, Ocular , Child , Disease Progression , Humans , Ophthalmic Solutions , Refraction, Ocular , Visual Acuity
18.
J Transl Med ; 19(1): 86, 2021 02 25.
Article En | MEDLINE | ID: mdl-33632240

BACKGROUND: Autoantibody production against endogenous cellular components is pathogenic feature of systemic lupus erythematosus (SLE). Follicular helper T (TFH) cells aid in B cell differentiation into autoantibody-producing plasma cells (PCs). The IL-6 and IL-21 cytokine-mediated STAT3 signaling are crucial for the differentiation to TFH cells. Niclosamide is an anti-helminthic drug used to treat parasitic infections but also exhibits a therapeutic effect on autoimmune diseases due to its potential immune regulatory effects. In this study, we examined whether niclosamide treatment could relieve lupus-like autoimmunity by modulating the differentiation of TFH cells in two murine models of lupus. METHODS: 10-week-old MRL/lpr mice were orally administered with 100 mg/kg of niclosamide or with 0.5% methylcellulose (MC, vehicle) daily for 7 weeks. TLR7 agonist, resiquimod was topically applied to an ear of 8-week-old C57BL/6 mice 3 times a week for 5 weeks. And they were orally administered with 100 mg/kg of niclosamide or with 0.5% MC daily for 5 weeks. Every mouse was analyzed for lupus nephritis, proteinuria, autoantibodies, immune complex, immune cell subsets at the time of the euthanization. RESULTS: Niclosamide treatment greatly improved proteinuria, anti-dsDNA antibody levels, immunoglobulin subclass titers, histology of lupus nephritis, and C3 deposition in MRL/lpr and R848-induced mice. In addition, niclosamide inhibited the proportion of TFH cells and PCs in the spleens of these animals, and effectively suppressed differentiation of TFH-like cells and expression of associated genes in vitro. CONCLUSIONS: Niclosamide exerted therapeutic effects on murine lupus models by suppressing TFH cells and plasma cells through STAT3 inhibition.


Lupus Erythematosus, Systemic , Niclosamide , Animals , Disease Models, Animal , Lupus Erythematosus, Systemic/drug therapy , Mice , Mice, Inbred C57BL , Mice, Inbred MRL lpr , Niclosamide/pharmacology , Niclosamide/therapeutic use , Severity of Illness Index , T Follicular Helper Cells , T-Lymphocytes, Helper-Inducer
19.
Br J Ophthalmol ; 105(1): 124-130, 2021 01.
Article En | MEDLINE | ID: mdl-32217540

AIMS: To evaluate the associations between retinal blood flow (RBF) and optical coherence tomography (OCT) structural measurements in normal-tension glaucoma (NTG) eyes with single-hemifield visual field (VF) damage by the Doppler OCT. METHODS: The Doppler OCT was used to measure temporal artery (TA) RBF and temporal vein (TV) RBF. Retinal nerve fibre layer thickness (RNFLT) was measured by spectral-domain OCT. RESULTS: Forty-three consecutive eyes of 43 patients with NTG with VF defect confined to a single hemifield and 24 eyes of 24 age-matched healthy subjects were studied. TA and TV RBF and RNFLT were reduced in the damaged hemisphere compared with the normal hemisphere (mean (SD), 3.61 (1.68) vs 5.86 (2.59) µL/min, p<0.001; 5.61 (2.51) vs 6.94 (2.83) µL/min, p=0.010; 69.0 (19.7) vs 99.7 (22.8) µm, p<0.001). Those values in the normal hemisphere of NTG eyes also decreased compared with the healthy hemisphere of the healthy eyes (8.40 (3.36) µL/min, p<0.001; 9.28 (4.47) µL/min, p<0.002; 122.8 (20.2) µm, p<0.001). Multivariate model showed that normal and damaged hemispheres and RNFLT were associated with RBF reduction. In addition, the RBF in the normal hemisphere was lower than that in the healthy hemisphere even after adjusting for RNFLT. CONCLUSION: In NTG eyes with single-hemifield damage, the RBF was significantly reduced in the damaged hemisphere compared with the normal one. The RBF decreased in the normal and damaged hemispheres of NTG eyes compared with the healthy hemisphere independent from RNFLT.


Hemianopsia/physiopathology , Low Tension Glaucoma/physiopathology , Retinal Vessels/physiopathology , Aged , Arterial Pressure/physiology , Blood Flow Velocity/physiology , Female , Gonioscopy , Hemianopsia/diagnosis , Humans , Intraocular Pressure/physiology , Low Tension Glaucoma/diagnosis , Male , Middle Aged , Nerve Fibers/pathology , Optic Disk/blood supply , Regional Blood Flow/physiology , Retinal Ganglion Cells/pathology , Tomography, Optical Coherence , Tonometry, Ocular , Ultrasonography, Doppler , Visual Field Tests , Visual Fields/physiology
20.
Ophthalmol Retina ; 5(5): 458-467, 2021 05.
Article En | MEDLINE | ID: mdl-32858246

PURPOSE: To describe the distribution and determinants of choroidal thickness (CT) in participants in a population study based on spectral-domain (SD)-OCT measurements. DESIGN: Population-based, cross-sectional study. PARTICIPANTS: Ethnic Chinese, Indian, and Malay adults aged more than 50 years without any retinal diseases (e.g., diabetic retinopathy, macular edema, age-related macular degeneration, central serous chorioretinopathy) that might affect the CT were recruited from the Singapore Epidemiology of Eye Diseases Study. METHODS: Choroidal imaging was performed by SD-OCT (Spectralis, Heidelberg Engineering, Heidelberg, Germany) in enhanced depth imaging (EDI) mode. Subfoveal choroidal thickness (SFCT) was measured on the foveal line scan by 2 retinal experts independently (YS and KT), and the average was used in the analyses. In Chinese and Indian cohorts in whom macular raster scans were captured, the manufacturer-supplied research software (Heyex SP-X version 6.4.8.116; Heidelberg Engineering) was used to obtain automated segmentation yielding mean choroidal thickness in each of the 9 ETDRS grid sectors. MAIN OUTCOME MEASURES: Subfoveal choroidal thickness and regional CT in the 9 ETDRS grid sectors. RESULTS: For the SFCT analysis, 2794 eyes of 1619 participants (Chinese, Indian, and Malay ) were included. The mean age was 60.9 years (standard deviation, 7.7), and 797 (49.2%) were male. Mean SFCT was 255.2 µm (standard deviation, 102.6). The normal range of SFCT was 106 to 447 µm (corresponding to 5th and 95th percentile limits of SFCT, respectively). In multivariable models, thinner SFCT was associated with older age, female gender, longer axial length, and Malay (vs. Chinese) ethnicity. In the subset of Chinese and Indian eyes (n = 1842) in whom regional variation was evaluated, the choroid was thickest at the superior and temporal sectors and thinner at the inferior and nasal sectors. CONCLUSIONS: Subfoveal choroidal thickness is influenced by age, gender, and ethnicity along with regional differences even within individual eyes. Subfoveal choroidal thickness also shows a wide range in physiologic limits. These data may be used as a reference in future studies.


Axial Length, Eye/diagnostic imaging , Choroid/diagnostic imaging , Ethnicity , Eye Diseases/diagnosis , Population Surveillance , Risk Assessment/methods , Tomography, Optical Coherence/methods , Cross-Sectional Studies , Eye Diseases/ethnology , Female , Follow-Up Studies , Humans , Incidence , Male , Middle Aged , Risk Factors , Singapore/epidemiology
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