Taurine: a promising nutraceutic in the prevention of retinal degeneration

Taurine is considered a non-essential amino acid because it is synthesized by most mammals.However,dietary intake of taurine may be necessary to achieve the physiological levels required for the development,maintenance,and function of certain tissues.Taurine may be especially important for the retina.The concentration of taurine in the retina is higher than that in any other tissue in the body and taurine deficiency causes retinal oxidative stress,apoptosis,and degeneration of photoreceptors and retinal ganglion cells.Low plasma taurine levels may also underlie retinal degeneration in humans and therefore,taurine administration could exert retinal neuroprotective effects.Taurine has antioxidant,anti-apoptotic,immunomodulatory,and calcium homeostasis-regulatory properties.This review summarizes the role of taurine in retinal health and disease,where it appears that taurine may be a promising nutraceutical.

Increased retinal venule diameter as a prognostic indicator for recurrent cerebrovascular events:a prospective observational study

Microvasculature of the retina is considered an alternative marker of cerebral vascular risk in healthy populations.However,the ability of retinal vasculature changes,specifically focusing on retinal vessel diameter,to predict the recurrence of cerebrovascular events in patients with ischemic stroke has not been determined comprehensively.While previous studies have shown a link between retinal vessel diameter and recurrent cerebrovascular events,they have not incorporated this information into a predictive model.Therefore,this study aimed to investigate the relationship between retinal vessel diameter and subsequent cerebrovascular events in patients with acute ischemic stroke.Additionally,we sought to establish a predictive model by combining retinal veessel diameter with traditional risk factors.We performed a prospective observational study of 141 patients with acute ischemic stroke who were admitted to the First Affiliated Hospital of Jinan University.All of these patients underwent digital retinal imaging within 72 hours of admission and were followed up for 3 years.We found that,after adjusting for related risk factors,patients with acute ischemic stroke with mean arteriolar diameter within 0.5-1.0 disc diameters of the disc margin(MAD_(0.5-1.0DD))of≥74.14μm and mean venular diameter within 0.5-1.0 disc diameters of the disc margin(MVD_(0.5-1.0DD))of≥83.91μm tended to experience recurrent cerebrovascular events.We established three multivariate Cox proportional hazard regression models:model 1 included traditional risk factors,model 2 added MAD_(0.5-1.0DD)to model 1,and model 3 added MVD0.5-1.0DD to model 1.Model 3 had the greatest potential to predict subsequent cerebrovascular events,followed by model 2,and finally model 1.These findings indicate that combining retinal venular or arteriolar diameter with traditional risk factors could improve the prediction of recurrent cerebrovascular events in patients with acute ischemic stroke,and that retinal imaging could be a useful and non-invasive method for identifying high-risk patients who require closer monitoring and more aggressive management.

Interplay between mesenchymal stromal cells and the immune system after transplantation: implications for advanced cell therapy in the retina

Advanced mesenchymal stromal cell-based therapies for neurodegenerative diseases are widely investigated in preclinical models.Mesenchymal stromal cells are well positioned as therapeutics because they address the underlying mechanisms of neurodegeneration,namely trophic factor deprivation and neuroinflammation.Most studies have focused on the beneficial effects of mesenchymal stromal cell transplantation on neuronal survival or functional improvement.However,little attention has been paid to the interaction between mesenchymal stromal cells and the host immune system due to the immunomodulatory properties of mesenchymal stromal cells and the long-held belief of the immunoprivileged status of the central nervous system.Here,we review the crosstalk between mesenchymal stromal cells and the immune system in general and in the context of the central nervous system,focusing on recent work in the retina and the importance of the type of transplantation.

P-aminobenzoic acid promotes retinal regeneration through activation of Ascl1a in zebrafish

The retina of zebrafish can regenerate completely after injury.M ultiple studies have demonstrated that metabolic alte rations occur during retinal damage;however to date no study has identified a link between metabolites and retinal regeneration of zebrafish.Here,we performed an unbiased metabolome sequencing in the N-methyl-D-aspartic acid-damaged retinas of zebrafish to demonstrate the metabolomic mechanism of retinal regeneration.Among the differentially-ex pressed metabolites,we found a significant decrease in p-aminobenzoic acid in the N-methyl-D-aspartic acid-damaged retinas of zebrafish.Then,we investigated the role of p-aminobenzoic acid in retinal regeneration in adult zebrafish.Impo rtantly,p-aminobenzoic acid activated Achaetescute complex-like 1a expression,thereby promoting Müller glia reprogramming and division,as well as Müller glia-derived progenitor cell proliferation.Finally,we eliminated folic acid and inflammation as downstream effectors of PABA and demonstrated that PABA had little effect on Müller glia distribution.Taken together,these findings show that PABA contributes to retinal regeneration through activation of Achaetescute complex-like 1a expression in the N-methyl-Daspartic acid-damaged retinas of zebrafish.

Homer1a reduces inflammatory response after retinal ischemia/reperfusion injury

Elevated intraocular pressure(IOP)is one of the causes of retinal ischemia/reperfusion injury,which results in NRP3 inflammasome activation and leads to visual damage.Homerla is repo rted to play a protective role in neuroinflammation in the cerebrum.However,the effects of Homerla on NLRP3inflammasomes in retinal ischemia/reperfusion injury caused by elevated IOP remain unknown.In our study,animal models we re constructed using C57BL/6J and Homer1^(flox/-)/Homerla^(+/-)/Nestin-Cre^(+/-)mice with elevated IOP-induced retinal ischemia/repe rfusion injury.For in vitro expe riments,the oxygen-glucose deprivation/repe rfusion injury model was constructed with M uller cells.We found that Homerla ove rexpression amelio rated the decreases in retinal thickness and Muller cell viability after ischemia/reperfusion injury.Furthermore,Homerla knockdown promoted NF-κB P65^(Ser536)activation via caspase-8,NF-κB P65 nuclear translocation,NLRP3 inflammasome formation,and the production and processing of interleukin-1βand inte rleukin-18.The opposite results we re observed with Homerla ove rexpression.Finally,the combined administration of Homerla protein and JSH-23 significantly inhibited the reduction in retinal thickness in Homer1^(flox/-)Homer1a^(+/-)/Nestin-Cre^(+/-)mice and apoptosis in M uller cells after ischemia/reperfusion injury.Taken together,these studies demonstrate that Homer1a exerts protective effects on retinal tissue and M uller cells via the caspase-8/NF-KB P65/NLRP3 pathway after I/R injury.

Circadian rhythm disruption and retinal dysfunction:a bidirectional link in Alzheimer’s disease?

Dysfunction in circadian rhythms is a common occurrence in patients with Alzheimer’s disease.A predominant function of the retina is circadian synchronization,carrying information to the brain through the retinohypothalamic tract,which projects to the suprachiasmatic nucleus.Notably,Alzheimer’s disease hallmarks,including amyloid-β,are present in the retinas of Alzheimer’s disease patients,followed/associated by structural and functional disturbances.However,the mechanistic link between circadian dysfunction and the pathological changes affecting the retina in Alzheimer’s disease is not fully understood,although some studies point to the possibility that retinal dysfunction could be considered an early pathological process that directly modulates the circadian rhythm.

Simulation of liquid cone formation on the tip apex of indium field emission electric propulsion thrusters

Field emission electric propulsion(FEEP) thrusters possess excellent characteristics, such as high specific impulse, low power requirements, compact size and precise pointing capabilities,making them ideal propulsion devices for micro-nano satellites. However, the detection of certain aspects, such as the evolution process of the liquid cone and the physical quantities at the cone apex, proves challenging due to the minute size of the needle tip and the vacuum environment in which they operate. Consequently, this paper introduces a computational fluid dynamics(CFD) model to gain insight into the formation process of the liquid cone on the tip apex of indium FEEP. The CFD model is based on electrohydrodynamic(EHD) equations and the volume of fluid(VOF) method. The entire cone formation process can be divided into three stages, and the time-dependent characteristics of the physical quantities at the cone apex are investigated. The influences of film thickness, apex radius size and applied voltage are compared.The results indicate a gradual increase in the values of electrostatic stress and surface tension stress at the cone apex over an initial period, followed by a rapid escalation within a short duration.Apex configurations featuring a small radius, thick film and high voltage exhibit a propensity for liquid cone formation, and the cone growth time decreases as the film thickness increases.Moreover, some unstable behavior is observed during the cone formation process.

Retinal displacement after surgery for idiopathic macular hole

AIM:To review and summarize the mechanism hypothesis,influencing factors and possible consequences of macular retinal displacement after idiopathic macular hole(IMH)surgery.METHODS:PubMed and Web of Science database was searched for studies published before April 2023 on“Retinal displacement”,“Idiopathic macular holes”,and“Macular displacement”.RESULTS:Recently,more academics have begun to focus on retinal displacement following idiopathic macular holes.They found that internal limiting membrane(ILM)peeling was the main cause of inducing postoperative position shift in the macular region.Moreover,several studies have revealed that the macular hole itself,as well as ILM peeling method,will have an impact on the result.In addition,this phenomenon is related to postoperative changes in macular retinal thickness,cone outer segment tips line recovery,the occurrence of dissociated optic nerve fiber layer(DONFL)and the degree of metamorphopsia.CONCLUSION:As a subclinical phenomenon,the clinical significance of postoperative macular displacement cannot be underestimated as it may affect the recovery of anatomy and function.

Microvascular alterations of the ocular surface and retina in connective tissue disease-related interstitial lung disease

AIM:To examine the disparities in macular retinal vascular density between individuals with connective tissue disease-related interstitial lung disease(CTD-ILD)and healthy controls(HCs)by optical coherence tomography angiography(OCTA)and to investigate the changes in microvascular density in abnormal eyes.METHODS:For a retrospective case-control study,a total of 16 patients(32 eyes)diagnosed with CTD-ILD were selected as the ILD group.The 16 healthy volunteers with 32 eyes,matched in terms of age and sex with the patients,were recruited as control group.The macular retina’s superficial retinal layer(SRL)and deep retinal layer(DRL)were examined and scanned using OCTA in each individual eye.The densities of retinal microvascular(MIR),macrovascular(MAR),and total microvascular(TMI)were calculated and compared.Changes in retinal vascular density in the macular region were analyzed using three different segmentation methods:central annuli segmentation method(C1-C6),hemispheric segmentation method[uperior right(SR),superior left(SL),inferior left(IL),and inferior right(IR)],and Early Treatment Diabetic Retinopathy Study(ETDRS)methods[superior(S),inferior(I),left(L),and right(R)].The data were analyzed using Version 9.0 of GraphPad prism and Pearson analysis.RESULTS:The OCTA data demonstrated a statistically significant difference(P<0.05)in macular retinal microvessel density between the two groups.Specifically,in the SRL and DRL analyses,the ILD group exhibited significantly lower surface density of MIR and TMI compared to the HCs group(P<0.05).Furthermore,using the hemispheric segmentation method,the ILD group showed notable reductions in SL,SR,and IL in the superficial retina(P<0.05),as well as marked decreases in SL and IR in the deep retina(P<0.05).Similarly,when employing the ETDRS method,the ILD group displayed substantial drops in superficial retinal S and I(P<0.05),along with notable reductions in deep retinal L,I,and R(P<0.05).In the central annuli segmentation method,the ILD group exhibited a significant decrease in the superficial retinal C2-4 region(P<0.05),whereas the deep retina showed a notable reduction in the C3-5 region(P<0.05).Additionally,there was an observed higher positive likelihood ratio in the superficial SR region and deep MIR.Furthermore,there was a negative correlation between conjunctival vascular density and both deep and superficial retinal TMI(P<0.001).CONCLUSION:Patients with CTD-ILD exhibits a significantly higher conjunctival vascular density compared to the HCs group.Conversely,their fundus retinal microvascular density is significantly lower.Furthermore,CTD-ILD patients display notably lower superficial and deep retinal vascular density in comparison to the HCs group.The inverse correlation between conjunctival vascular density and both superficial and deep retinal TMI suggests that detecting subtle changes in ocular microcirculation could potentially serve as an early diagnostic indicator for connective tissue diseases,thereby enhancing disease management.

Single-cell RNA sequencing analysis of the retina under acute high intraocular pressure

High intraocular pressure causes retinal ganglion cell injury in primary and secondary glaucoma diseases,yet the molecular landscape characteristics of retinal cells under high intraocular pressure remain unknown.Rat models of acute hypertension ocular pressure were established by injection of cross-linked hyaluronic acid hydrogel(Healaflow■).Single-cell RNA sequencing was then used to describe the cellular composition and molecular profile of the retina following high intraocular pressure.Our results identified a total of 12 cell types,namely retinal pigment epithelial cells,rod-photoreceptor cells,bipolar cells,Müller cells,microglia,cone-photoreceptor cells,retinal ganglion cells,endothelial cells,retinal progenitor cells,oligodendrocytes,pericytes,and fibroblasts.The single-cell RNA sequencing analysis of the retina under acute high intraocular pressure revealed obvious changes in the proportions of various retinal cells,with ganglion cells decreased by 23%.Hematoxylin and eosin staining and TUNEL staining confirmed the damage to retinal ganglion cells under high intraocular pressure.We extracted data from retinal ganglion cells and analyzed the retinal ganglion cell cluster with the most distinct expression.We found upregulation of the B3gat2 gene,which is associated with neuronal migration and adhesion,and downregulation of the Tsc22d gene,which participates in inhibition of inflammation.This study is the first to reveal molecular changes and intercellular interactions in the retina under high intraocular pressure.These data contribute to understanding of the molecular mechanism of retinal injury induced by high intraocular pressure and will benefit the development of novel therapies.

Postnatal development of rat retina:a continuous observation and comparison between the organotypic retinal explant model and in vivo development

The organotypic retinal explant culture has been established for more than a decade and offers a range of unique advantages compared with in vivo experiments and cell cultures.However,the lack of systematic and continuous comparison between in vivo retinal development and the organotypic retinal explant culture makes this model controversial in postnatal retinal development studies.Thus,we aimed to verify the feasibility of using this model for postnatal retinal development studies by comparing it with the in vivo retina.In this study,we showed that postnatal retinal explants undergo normal development,and exhibit a consistent structure and timeline with retinas in vivo.Initially,we used SOX2 and PAX6 immunostaining to identify retinal progenitor cells.We then examined cell proliferation and migration by immunostaining with Ki-67 and doublecortin,respectively.Ki-67-and doublecortin-positive cells decreased in both in vivo and explants during postnatal retinogenesis,and exhibited a high degree of similarity in abundance and distribution between groups.Additionally,we used Ceh-10 homeodomain-containing homolog,glutamate-ammonia ligase(glutamine synthetase),neuronal nuclei,and ionized calcium-binding adapter molecule 1 immunostaining to examine the emergence of bipolar cells,Müller glia,mature neurons,and microglia,respectively.The timing and spatial patterns of the emergence of these cell types were remarkably consistent between in vivo and explant retinas.Our study showed that the organotypic retinal explant culture model had a high degree of consistency with the progression of in vivo early postnatal retina development.The findings confirm the accuracy and credibility of this model and support its use for long-term,systematic,and continuous observation.

Microstructures and formation mechanism of headstand pyrocarbon cones developed by electromagnetic-field-assisted CVD

Novel headstand pyrocarbon cones （HPCs） with hollow structure were developed on the surfaces of pyrocarbon layers of the carbon/carbon （C/C） composites at 650-750 °C by the electromagnetic-field-assisted chemical vapor deposition in the absence of catalysts. The fine microstructures of the HPCs were characterized by high-resolution transmission electron microscopy. The results show that the textural features of the HPCs directly transfer from turbostratic structure in roots to a well-ordered high texture in stems. And the degree of high texture ordering decreases gradually from the stem to the tail of the HPCs. The formation mechanism of the HPCs was inferred as the comprehensive effect of polarization induction on electromagnetic fields and particle-filler property under disruptive discharge.

ANALYSIS ON THE SPINNING FORCES IN FLEXIBLE SPINNING OF CONES

Flexible spinning is a new type of spinning process where spin-forming isperformed without using a mandrel. Combining shearing and rolling processes, the calculationformulas of the spinning forces in flexible spinning of cones is presented. The effects of the mainprocessing parameters, such as gripping force G applied to the blank by the inner roller, the feedrate of rollers f and the roundness radius of outer roller r_o, on the spinning forces are analyzedexperimentally and theoretically.

Inflow boundary condition for DNS of turbulent boundary layers on supersonic blunt cones

For direct numerical simulation （DNS） of turbulent boundary layers, generation of an appropriate inflow condition needs to be considered. This paper proposes a method, with which the inflow condition for spatial-mode DNS of turbulent boundary layers on supersonic blunt cones with different Mach numbers, Reynolds numbers and wall temperature conditions can be generated. This is based only on a given instant flow field obtained by a temporal-mode DNS of a turbulent boundary layer on a flat plate. Effectiveness of the method is shown in three typical examples by comparing the results with those obtained by other methods.

Secondary Cones of the Shatsky Rise and Implications for Late-Stage Volcanism Atop Oceanic Plateaus

Oceanic plateaus are large igneous provinces in the oceans,created by massive underwater eruptions,but their late-stage volcanism is poorly understood.With the addition of recent high-quality bathymetric data to existing data,286 secondary cones were discovered over Shatsky Rise oceanic plateau.These cones with steeper flank slopes(mean 6.1°±4.4°)and smaller sizes(102–1923 m in height)are morphologically distinct from the plateau,and they are thought to have formed after the main volcanic episodes.Cone height and characteristic height(420 m)are close to seamounts in the Pacific Ocean,whereas greater than those in the Atlantic Ocean.Mean flatness of Shatsky Rise’s cones(0.25±0.20)are similar to that of seamounts in both Pacific and Atlantic Oceans,but notably density in cone distribution(0.56 km^-3)and their mean slope are significantly lower than those of seamounts in the two oceans.Lower slopes of secondary cones within Shatsky Rise may be explained by higher effusion rates of remaining magma.Although cone formation was expected to have a link to rifting by seafloor spreading,weak relationship between cone orientation and magnetic anomaly pattern implies that the expectation is negative.Moreover,weak correlation between the cone height and depth indicates it is not true that volcanic cones grow taller when they occur closer to the massif summits with thicker oceanic crust,which was suggested as the increase in hydraulic pressure.Cone height and flatness are also not strongly related,implying that remaining magma supply was too limited to foster the cones to critical height.

THE INVARIANT CLOSED CONES OF HOMOGENEOUS VECTOR FIELDS OF DEGREE TWO IN R^(3)

In this paper, the authors investigate the invariant cones of quadratic homoge- neous polynomial vector fields in three variables. Necessary and sufficient conditions for the existence of non-isolated invariant closed cones are obtained by the algebraic expressions in terms of the coefficients of certain quadratic homogeneous polynomials.

Smoothing Newton Algorithm for Linear Programming over Symmetric Cones

By using the theory of Euclidean Jordan algebras,based on a new class of smoothing functions,the QiSun-Zhou's smoothing Newton algorithm is extended to solve linear programming over symmetric cones(SCLP).The algorithm is globally convergent under suitable assumptions.

ELASTICITY SOLUTIONS OF SPHERICALLY ISOTROPIC CONES UNDER CONCENTRATED LOADS AT APEX

Based on the Ref [9]the displacement and stress distributions in a spherically isotropic cone subjected to concentrated loads at apex are studied The displacementand stresses are given explicitly for the cone in compression torsion and bending cases respectively based on the situation of the concentrated forces and moments Finally.the hollow cone problems are discussed .

CHARACTERIZATION OF SOLID CONES

The author gives a dual characterization of solid cones in locally convex spaces. From this the author obtains some criteria for judging convex cones to be solid in various kinds of locally convex spaces. Using a general expression of the interior of a solid cone, the author obtains a number of necessary and sufficient conditions for convex cones to be solid in the framework of Banach spaces. In particular, the author gives a dual relationship between solid cones and generalized sharp cones. The related known results are improved and extended.

Inflammation and retinal degenerative diseases

Vision is an ability that depends on the precise structure and functioning of the retina.Any kind of stress or injury can disrupt the retinal architecture and leads to vision impairment,vision loss,and blindness.Immune system and immune response function maintain homeostasis in the microenvironment.Several genetic,metabolic,and environmental factors may alter retinal homeostasis,and these events may initiate various inflammatory cascades.The prolonged inflammatory state may contribute to the initiation and development of retinal disorders such as glaucoma,age-related macular degeneration,diabetic retinopathy,and retinitis pigmentosa,which pose a threat to vision.In the current review,we attempted to provide sufficient evidence on the role of inflammation in these retinal disorders.Moreover,this review paves the way to focus on therapeutic targets of the disease,which are found to be promising.