Aqueous Pathway Research Articles

High-Resolution Modeling of Aqueous Humor Dynamics in the Conventional Outflow Pathway of a Normal Human Donor Eye

Background and Objective: The conventional aqueous outflow pathway, which includes the trabecular meshwork (TM), juxtacanalicular tissue (JCT), and inner wall endothelium of Schlemm's canal (SC) and its basement membrane, plays a significant role in regulating intraocular pressure (IOP) by controlling aqueous humor outflow resistance. Despite its significance, the biomechanical and hydrodynamic properties of this region remain inadequately understood. Fluid-structure interaction (FSI) and computational fluid dynamics (CFD) modeling using high-resolution microstructural images of the outflow pathway provides a comprehensive method to estimate these properties under varying conditions, offering valuable understandings beyond the capabilities of current imaging techniques.Methods: In this study, we utilized high-resolution 3D serial block-face scanning electron microscopy (SBF-SEM) to image the TM/JCT/SC complex of a normal human donor eye perfusion-fixed at an IOP of 7 mm Hg. We developed a detailed 3D finite element (FE) model of the pathway using SBF-SEM images to simulate the biomechanical environment. The model included the TM/JCT/SC complex (structure) with interspersed aqueous humor (fluid). We employed a 3D, inverse FE algorithm to calculate the unloaded geometry of the TM/JCT/SC complex and utilized FSI to simulate the pressurization of the complex from 0 to 15 mm Hg.Results: Our simulations revealed that the resultant velocity distribution in the aqueous humor across the TM/JCT/SC complex is heterogeneous. The JCT and its deepest regions, specifically the basement membrane of the inner wall of SC, exhibited a volumetric average velocity of ∼0.011 mm/s, which is higher than the TM regions, with a volumetric average velocity of ∼0.007 mm/s. Shear stress analysis indicated that the maximum shear stress, based on our FE code criteria, was 0.5 Pa starting from 10 µm into the TM from the anterior chamber and increased to 0.95 Pa in the JCT and its adjacent SC inner wall basement membrane. Also, the tensile stress and strain distributions showed significant variations, with the first principal stress reaching up to 57 Pa (compressive volumetric average) and the first principal strain reaching up to 3.5% in areas of high mechanical loading. The resultant stresses, strains, and velocities exhibited relatively similar average values across the TM, JCT, and SC regions, primarily due to the uniform elastic moduli assigned to these components. Our computational fluid dynamics (CFD) analysis revealed that while the velocity of the aqueous humor remained consistent, the maximum shear stress was reduced by a factor of thirty.Conclusion: The uneven distribution of shear stress and velocity within the TM/JCT/SC complex highlights the complex biomechanical environment that regulates aqueous humor outflow.

Aqueous Humor Angiography.

Aqueous humor angiography, or aqueous angiography, is an anterior segment imaging technique capable of visualizing the conventional/trabecular aqueous humor outflow pathways. As a translational technique, it is applicable for in vivo imaging in living subjects and ex vivo imaging using whole-globe preparations or anterior segment perfusion setups. Excellent spatial and temporal resolution has enabled insights into the segmental distribution of aqueous humor outflow in physiological conditions as well as after trabecular bypass surgery. In this chapter, we thoroughly describe aqueous humor angiography in various experimental setups. The necessary materials for different settings and their application for in vivo and ex vivo experiments as well as notes on dye choice, dye sequences, and special considerations on performing aqueous humor angiography during surgery are presented.

Evaluation of Cross-Linked Actin Networks (CLANs) in Human Trabecular Meshwork Cells and Tissues.

Elevated intraocular pressure (IOP) is a major risk factor for the development and progression of glaucoma, the leading cause of irreversible vision loss and blindness. An overall increase in resistance to aqueous humor outflow causes sustained elevation in IOP. Glaucomatous insults in the aqueous humor outflow pathway, including the trabecular meshwork (TM), precede such chronic physiological changes in IOP. These insults include ultrastructural changes with excessive extracellular matrix deposition and actin cytoskeletal reorganization that leads to pathological stiffening of the ocular tissues. One of the most common cytoskeletal changes associated with TM tissue stiffness in glaucoma is the increased prevalence of cross-linked actin networks (CLANs) in cells of the trabecular meshwork (TM) and lamina cribrosa (LC). In glaucomatous cells, rearrangement of linear actin stress fibers leads to formation of polygonal arrays within the cytoplasm, resembling a geodesic dome-like structure, that we identified as CLANs. In addition to increased amounts of CLANs in POAG TM cells and tissues, we also discovered that glucocorticoid (GC) and TGFβ2 signaling pathways associated with the development of ocular hypertension (OHT) and glaucoma also induced CLANs in the TM. Despite a clear association, we are yet to completely understand the mechanisms involved in CLAN formation and their direct relevance to disease pathology. In this chapter, we will describe methods to identify and characterize CLANs using fluorescent microscopy in primary TM cell cultures, ex vivo perfusion cultured human anterior segments, and in situ in human donor eyes.

Green-Light-Triggered and Self-Calibrated Cascade Release of Nitric Oxide and Carbon Monoxide for Synergistic Glaucoma Therapy.

Glaucoma is an optic degenerative neuropathy that is driven by a vicious cycle of oxidative stress and mechanical stress. Current clinical treatments aim exclusively at alleviating mechanical stress by reducing the intraocular pressure (IOP). With the unattended oxidative stress, recurrence and deterioration of mechanical stress are inevitable. Nitric oxide (NO) and carbon monoxide (CO) are endogenous gaseous signaling molecules for vasodilation and anti-inflammation, respectively. Mounting evidence suggests an intricate interplay between NO and CO to mediate their biological roles, like how it takes two to dance a waltz. This leads to the concept of "gas waltz therapy" for glaucoma, in which NO is released to reduce IOP and stoichiometric CO is coreleased to suppress oxidative stress. CND570 is the first phototriggered cascade NO/CO donor, to the best of our knowledge. Notably, the release of NO/CO is accompanied by the concomitant release of a rhodamine dye whose bright fluorescence is harnessed as a convenient calibration mechanism of the gas release profile. CND570 exhibits excellent transcorneal permeability and reaches the target aqueous humor outflow pathway. Further, green-light irradiation triggers release of CO and NO in the eye tissue of glaucoma mice. NO and CO could promote the upregulation of soluble guanylate cyclase (sGC) in both in vitro and in vivo models. Notably, CND570 treatment significantly reduces the oxidative stress associated with glaucoma. NO/CO-based gas waltz therapy is a promising new avenue for glaucoma treatment.

Focusing on issues about phacoemulsification lens extraction combined with goniosynechialysis

Angle closure is a basic pathological process in primary angle-closure glaucoma. Unlike filtration anti-glaucoma surgery, goniosynechialysis is a treatment for the cause of primary angle-closure glaucoma by reconstructing the physiological aqueous outflow pathway. In the past 10 years, phacoemulsification lens extraction with posterior chamber intraocular lens implantation in combination with goniosynechialysis for the treatment of primary angle-closure glaucoma has become a hot topic of clinical research and discussion. This article points out the issues that need to be paid attention to in the clinical practice of the combined surgery, including the relationship between phacoemulsification surgery and goniosynechialysis, the effectiveness and influencing factors of the combined surgery, and how to avoid the postoperative re-adhesion of the angle, in order to provide reference and guidance for better goniosynechialysis.

Visualization of Scleral Flap Patency in Glaucoma Filtering Blebs Using OCT

PurposeTo investigate the use of anterior segment-optical coherence tomography (AS-OCT) to visualise the aqueous outflow pathway and patency of the scleral flap in glaucoma filtration surgery blebs. DesignCross-sectional study Subjects205 filtering blebs of 112 patients with glaucoma who had undergone trabeculectomy (Trab, n = 97) or deep sclerectomy surgery (DS, n = 108) with/without mitomycin-C (MMC). MethodsSwept source AS-OCT raster slices were used to image the Trab and DS blebs in sagittal and coronal planes using a standardised protocol. Bleb appearances were classified into four categories based on the scleral flap and sclerostomy/TDW appearance; A—sclerostomy/TDW not visible, B—sclerostomy/TDW visible but scleral flap indiscriminate from sclera, C—scleral flap distinct but edges adherent to surrounding sclera, D—scleral flap edges non adherent to surrounding sclera. Surgical outcomes were classified into complete success (CS; IOP ≤18mmHg with no medications), qualified success (IOP ≤18 with medications) and failure (IOP>18mmHg). ResultsThe proportions of complete success, qualified success and failure in the Trab and DS cohorts were 45.0% and 29.6%, 33.0% and 31.5%, and 22.0% and 38.9% respectively, with a median post-operative follow up of 8.4 years (SD 7.9, IQR 3.2-9.0). In qualified success and failed blebs, category C (Trab, 53.7%; DS, 52.5%) accounted for the majority of scleral flap appearances, followed by categories A and B. Category D (86.0%; 71.9%) accounted for the majority of appearances in Trab and DS blebs with complete success. There was a significantly greater proportion of MMC use in categories C and D compared to categories A and B in both Trab (p < 0.0001) and DS (p = 0.02) cohorts, demonstrating the association of intraoperative MMC use with increased patency of the scleral flap. ConclusionSwept source AS-OCT may be used to visualise the position and patency of the sclerostomy/TDW and scleral flap in relation to surrounding structures in both sagittal and coronal planes. While free scleral flap edges are primarily correlated with MMC use, it may also correlate with surgical success. AS-OCT may be used to complement subjective bleb grading at the slit-lamp in the assessment of filtering blebs.

Biokinetics of Americium-241 in the euryhaline diamond sturgeon Acipenser gueldenstaedtii following its uptake from water or food

Americium-241 whole body and internal biokinetics were experimentally investigated in the euryhaline diamond sturgeon Acipenser gueldenstaedtii during its uptake from water and food, in fresh (FW) and brackish water (BW; 9 psu). Whole-body uptake rates of 241Am from water and subsequent depuration rates were quantified over 14 and 28 days, respectively, and assimilation efficiency (AE) of 241Am from diet (chironomid) was determined over 28 days. FW reduced the biological half-life of 241Am following aqueous uptake by an order of magnitude. In contrast BW greatly reduced 241Am assimilation efficiency (AE) from diet (chironomid) by several orders of magnitude (from an AE of 8.5% (FW) down to 0.003% (BW)). Hence, salinity per se is indicated as a major environmental variable in determining the radiological exposure of A. gueldenstaedtii to 241Am. During aqueous exposure BW appreciably increased 241Am activity concentrations in most body components, but aqueous or dietary exposure pathway at either salinity did not determine marked differences in how 241Am was distributed among six body components. The highly mineralized skin of A. gueldenstaedtii recurred as a major repository of 241Am in all experimental treatments, as high as 50% among body components, due to its internal transfer from diet, surface adsorption and/or active absorption from water. The indicated prominence of the aqueous, compared to the dietary, exposure pathway for 241Am accumulation by A. gueldenstaedtii suggests its radiological exposure would be enhanced by BW as it leads to its greater long-term retention, due to a much longer biological half-life.

Progression to bilaterality in unilateral primary congenital glaucoma

PurposeTo evaluate the incidence of rise in intraocular pressure (IOP) in fellow eyes of patients with unilateral primary congenital glaucoma (PCG) and to identify risk factors for IOP increase over long-term follow-up. MethodsThe medical records of unilateral PCG patients who had completed at least 5 years of follow-up were reviewed retrospectively. The incidence of developing ocular hypertension / glaucoma in fellow eyes was analyzed. Fellow eye progressors were those which showed an increase in optic nerve cupping by at least 0.2 since the first presentation or had IOP of >21 mm Hg on two occasions. The risk factors for progression that were analyzed included IOP, visual acuity, axial length, central corneal thickness (CCT), corneal diameters (CD), presence or absence of angle dysgenesis on high-resolution anterior segment optical coherence tomography (AS-OCT), and morphology of aqueous outflow pathways. ResultsAfter a median follow-up of 8.2 years (range, 5-25.5) progression to bilateral disease was found in 17 of 54 patients (32%), of whom 8 (15%) developed ocular hypertension and 9 (17%) developed glaucoma in the fellow eye. Among the unaffected fellow eyes, those with a larger CD (>12 mm), measured after at least 5 years’ follow-up, were ten times more likely to progress (P = 0.01; OR = 9.5 [95% CI, 1.7-54.3]). The presence of a patent supraciliary channel was significantly more frequently associated in fellow eyes compared with affected eyes on AS-OCT (OR = 1.4 [95% CI, 0.46-4.68]). ConclusionsOne-third of unaffected fellow eyes of unilateral PCG eventually progress over time, most often after 5 years. Larger CD at follow-up in the fellow eye is strongly predictive for progression.

Hydrogen peroxide serves as pivotal fountainhead for aerosol aqueous sulfate formation from a global perspective

Traditional atmospheric chemistry posits that sulfur dioxide (SO2) can be oxidized to sulfate (SO42–) through aqueous-phase reactions in clouds and gas-phase oxidation. Despite adequate knowledge of traditional mechanisms, several studies have highlighted the potential for SO2 oxidation within aerosol water. Given the widespread presence of tropospheric aerosols, SO42− production through aqueous-phase oxidation in aerosol water could have a pervasive global impact. Here, we quantify the potential contributions of aerosol aqueous pathways to global sulfate formation based on the GEOS-Chem simulations and subsequent theoretical calculations. Hydrogen peroxide (H2O2) oxidation significantly influences continental regions both horizontally and vertically. Over the past two decades, shifts in the formation pathways within typical cities reveal an intriguing trend: despite reductions in SO2 emissions, the increased atmospheric oxidation capacities, like rising H2O2 levels, prevent a steady decline in SO42− concentrations. Abating oxidants would facilitate the benefit of SO2 reduction and the positive feedback in sulfate mitigation.

To discuss the minimally invasive glaucoma surgery related to trabeculotomy from the perspective of physiological function of trabecular meshwork drainage pathway

The advent of minimally invasive glaucoma surgery (MIGS) has broadened the therapeutic options for managing glaucoma. In recent years, MIGS procedures targeting the trabecular meshwork-Schlemm's canal aqueous outflow resistance site have garnered significant attention. This focus has extended to the pathophysiological changes occurring within the aqueous outflow pathway. However, questions persist regarding the efficacy of near-peripheral or peripheral trabeculotomy in achieving the anticipated reduction of outflow resistance and the suitability of MIGS surgery for patients with primary open-angle glaucoma. By integrating clinical experience with pertinent clinical research, this paper advocates for a reevaluation of MIGS procedures to aid clinicians in making informed decisions regarding various glaucoma surgical interventions.

A Histomorphometric and Computational Investigation of the Stabilizing Role of Pectinate Ligaments in the Aqueous Outflow Pathway.

Murine models are commonly used to study glaucoma, the leading cause of irreversible blindness. Glaucoma is associated with elevated intra-ocular pressure (IOP), which is regulated by the tissues of the aqueous outflow pathway. In particular, pectinate ligaments (PLs) connect the iris and trabecular meshwork (TM) at the anterior chamber angle, with an unknown role in maintenance of the biomechanical stability of the aqueous outflow pathway, thus motivating this study. We conducted histomorphometric analysis and optical coherence tomography-based finite element (FE) modeling on three cohorts of C57BL/6 mice: "young" (2-6 months), "middle-aged" (11-16 months), and "elderly" (25-32 months). We evaluated the age-specific morphology of the outflow pathway tissues. Further, because of the known pressure-dependent Schlemm's canal (SC) narrowing, we assessed the dependence of the SC lumen area on varying IOPs in age-specific FE models over a physiological range of TM/PL stiffness values. We found age-dependent changes in morphology of outflow tissues; notably, the PLs were more developed in older mice compared to younger ones. In addition, FE modeling demonstrated that murine SC patency is highly dependent on the presence of PLs and that increased IOP caused SC collapse only with sufficiently low TM/PL stiffness values. Moreover, the elderly model showed more susceptibility to SC collapse compared to the younger models. In conclusion, our study elucidated the previously unexplored role of PLs in the aqueous outflow pathway, indicating their function in supporting TM and SC under elevated IOP.

Comparative analysis of traction forces in normal and glaucomatous trabecular meshwork cells within a 3D, active fluid-structure interaction culture environment

This study presents a 3D in vitro cell culture model, meticulously 3D printed to replicate the conventional aqueous outflow pathway anatomical structure, facilitating the study of trabecular meshwork (TM) cellular responses under glaucomatous conditions. Glaucoma affects TM cell functionality, leading to extracellular matrix (ECM) stiffening, enhanced cell-ECM adhesion, and obstructed aqueous humor outflow. Our model, reconstructed from polyacrylamide gel with elastic moduli of 1.5 and 21.7 kPa, is based on serial block-face scanning electron microscopy images of the outflow pathway. It allows for quantifying 3D, depth-dependent, dynamic traction forces exerted by both normal and glaucomatous TM cells within an active fluid-structure interaction (FSI) environment. In our experimental design, we designed two scenarios: a control group with TM cells observed over 20 hours without flow (static setting), focusing on intrinsic cellular contractile forces, and a second scenario incorporating active FSI to evaluate its impact on traction forces (dynamic setting). Our observations revealed that active FSI results in higher traction forces (normal: 1.83-fold and glaucoma: 2.24-fold) and shear strains (normal: 1.81-fold and glaucoma: 2.41-fold), with stiffer substrates amplifying this effect. Glaucomatous cells consistently exhibited larger forces than normal cells. Increasing gel stiffness led to enhanced stress fiber formation in TM cells, particularly in glaucomatous cells. Exposure to active FSI dramatically altered actin organization in both normal and glaucomatous TM cells, particularly affecting cortical actin stress fiber arrangement. This model while preliminary offers a new method in understanding TM cell biomechanics and ECM stiffening in glaucoma, highlighting the importance of FSI in these processes. Statement of significanceThis pioneering project presents an advanced 3D in vitro model, meticulously replicating the human trabecular meshwork's anatomy for glaucoma research. It enables precise quantification of cellular forces in a dynamic fluid-structure interaction, a leap forward from existing 2D models. This advancement promises significant insights into trabecular meshwork cell biomechanics and the stiffening of the extracellular matrix in glaucoma, offering potential pathways for innovative treatments. This research is positioned at the forefront of ocular disease study, with implications that extend to broader biomedical applications.

Reduced Aqueous Humor Outflow Pathway Arborization in Childhood Glaucoma Eyes.

To compare aqueous humor outflow (AHO) pathway patterns between eyes of childhood glaucoma patients and non-glaucomatous patients receiving cataract surgery. Aqueous angiography was performed in childhood glaucoma eyes (n = 5) receiving glaucoma surgery and in pediatric (n = 1) and healthy adult (n = 5) eyes receiving cataract surgery. Indocyanine green (0.4%) was introduced into the anterior chamber, and AHO was imaged using an angiographic camera (SPECTRALIS HRA+OCT with Flex Module). Images were acquired and analyzed (ImageJ with Analyze Skeleton 2D/3D plugin) from the nasal sides of the eyes, the usual site of glaucoma angle procedures. Image analysis endpoints included AHO vessel length, maximum vessel length, number of branches, number of branch junctions, and vessel density. Qualitatively, childhood glaucoma eyes demonstrated lesser AHO pathway arborization compared to pediatric and adult eyes without glaucoma. Quantitatively, childhood glaucoma and healthy adult cataract eyes showed similar AHO pathway average branch lengths and maximum branch lengths (P = 0.49-0.99). However, childhood glaucoma eyes demonstrated fewer branches (childhood glaucoma, 198.2 ± 35.3; adult cataract, 506 ± 59.5; P = 0.002), fewer branch junctions (childhood glaucoma, 74.6 ± 13.9; adult cataract, 202 ± 41.2; P = 0.019), and lower vessel densities (childhood glaucoma, 8% ± 1.4%; adult cataract, 17% ± 2.5%; P = 0.01). Childhood glaucoma patients demonstrated fewer distal AHO pathways and lesser AHO pathway arborization. These anatomical alternations may result in a new source of trabecular meshwork-independent AHO resistance in this disease cohort. Elevated distal outflow pathway resistance due to decreased AHO pathway arborization may explain some cases of failed trabecular bypass surgery in childhood glaucoma.

Thermodynamic property estimations for aqueous primary, secondary, and tertiary alkylamines, benzylamines, and their corresponding aminiums across temperature and pressure are validated by measurements from experiments

On Earth and beyond, organic chemistry often occurs in the presence of water within environments that deviate drastically from ambient conditions (25 °C and 1 bar). Accurately predicting aqueous organic reaction pathways is crucial toward understanding planetary scale processes such as the cycling of elements crucial for life (e.g., carbon and nitrogen). Advanced thermodynamic modeling can be utilized to determine the favorability of various organic reactions based on geologically relevant ranges of temperature and pressure, as well as compositional variables (e.g., pH). However, data that would otherwise allow for a diversity of organic compounds and environmental conditions to be modeled are sparse and rarely tested with experiments, particularly with regard to organic-nitrogen compounds. In this work, we develop a framework to estimate thermodynamic properties at ambient conditions that can then be extrapolated across ranges of temperature and pressure for aqueous primary, secondary, and tertiary amines and aminiums (protonated amines), specifically those structures containing linear alkyl chains and benzyl functional groups. We also performed hydrothermal experiments (250 °C, ∼40 bar) involving reactions of methylamines to test our resulting thermodynamic models, and we compare our models for other alkylamines and benzylamines to previous empirical measurements from the literature. Specifically, we use existing thermodynamic data along with our estimates at ambient conditions in combination with a variety of existing extrapolation methods related to the revised Helgeson-Kirkham-Flowers (HKF) equations of state to generate temperature- and pressure-dependent predictions of acid dissociation constants (i.e., pKa values) that strongly agree with previous empirical measurements. We use similar methods to predict product distributions for reactions involving primary, secondary, and tertiary amines/aminiums, as well as ammonia/ammonium and corresponding alcohols whose collective distributions depend on reversible substitution reactions. Our predictions are in good agreement with our experimental results involving the methylamine reaction system as well as previous experiments involving the benzylamine reaction system, for which we also produced thermodynamic estimates involving benzyl alcohol. The agreement between independent theoretical predictions and experimental measurements suggests that our estimated properties can be applied to modeling amine chemistry in other experimental and natural aqueous systems that range in temperature and pressure, providing new tools for planetary exploration.

Direct aqueous photochemistry of methylglyoxal and its effect on sulfate formation

In recent years, among many oxidation pathways studied for atmospheric sulfate formation, the aqueous phase oxidation pathways of H2O2 and organic hydroperoxides (ROOHs) have attracted great scientific attention. Higher concentrations of H2O2 and ubiquitous ROOHs have been observed in atmospheric aqueous phase environments (cloud water, fog droplets, etc.). However, there are still some gaps in the study of their aqueous phase generation and their influences on sulfate formation. In this study, the aqueous phase photochemical reaction of methylglyoxal, a ubiquitous organic substance in the atmospheric aqueous phase, was studied under UV irradiation, and the generation of H2O2 and ROOHs in this system was investigated. It is found for the first time that the aqueous phase photolysis of methylglyoxal not only produces H2O2 but also produces ROOHs, and UV light and O2 are necessary for the formation of H2O2 and ROOHs. Based on the experimental results, the possible mechanism of aqueous phase photochemistry of methylglyoxal and the generation of H2O2 and ROOHs were proposed. The effect of aqueous phase photolysis of methylglyoxal on sulfate formation under different conditions was also investigated. The results show that the aqueous phase photolysis of methylglyoxal significantly promoted SO2 oxidation and sulfate formation, in which SO2 oxidation was realized by the generated H2O2, ROOHs and •OH radicals, and the importance of the formed ROOHs cannot be ignored. These results fill some gaps in the field of aqueous phase H2O2 and ROOHs production, and to a certain extent confirm the important roles of the aqueous phase photolysis of methylglyoxal and the formed H2O2 and ROOHs in the production of sulfate. The study reveals the new sources of H2O2 and ROOHs, and provides a new insight into the heterogeneous aqueous phase oxidation pathways and mechanisms of SO2 in cloud and fog droplets and haze particles.

Investigating acquisition of magnetic properties and biocompatibility of Gadolinium substituted Strontium phosphosilicate for magnetic imaging in orthopaedics

The ability to acquire in situ magnetic resonance properties in biological apatites to facilitate real time MRI was investigated by substituting a series of hierarchically increasing Gadolinium over Strontium in the study. Samples were synthesized using an aqueous sol–gel pathway to ensure maximum reactivity and favour Silica-based species. Structural features were investigated using diffraction and IR spectra followed by VSM to calculate magnetization as a function of the field revealing the paramagnetic behaviour of the samples when doped. Morphological features visualized through FE-SEM showed sustained structural integrity of parent material characteristic of the P63/M space group and the EDAX spectra confirmed the hypothesised substitution when sintered as well. When immersed with SBF a loss of secondary phases and formation of amorphous calcium phosphate flakes were confirmed by diffraction and morphological studies. Biocompatibility was evaluated against first contact cells i.e. RBC via haemolytic study and L929 cells wherein Alamar assay show the samples least toxic at 25 μg/ml beyond which cell viability decreases providing enough evidence of applicability of Strontium phosphosilicate as a bioactive ceramic.

Integrating genetic regulation and single-cell expression with GWAS prioritizes causal genes and cell types for glaucoma

Primary open-angle glaucoma (POAG), characterized by retinal ganglion cell death, is a leading cause of irreversible blindness worldwide. However, its molecular and cellular causes are not well understood. Elevated intraocular pressure (IOP) is a major risk factor, but many patients have normal IOP. Colocalization and Mendelian randomization analysis of >240 POAG and IOP genome-wide association study (GWAS) loci and overlapping expression and splicing quantitative trait loci (e/sQTLs) in 49 GTEx tissues and retina prioritizes causal genes for 60% of loci. These genes are enriched in pathways implicated in extracellular matrix organization, cell adhesion, and vascular development. Analysis of single-nucleus RNA-seq of glaucoma-relevant eye tissues reveals that the POAG and IOP colocalizing genes and genome-wide associations are enriched in specific cell types in the aqueous outflow pathways, retina, optic nerve head, peripapillary sclera, and choroid. This study nominates IOP-dependent and independent regulatory mechanisms, genes, and cell types that may contribute to POAG pathogenesis.

Wintertime fine aerosol particles composition and its evolution in two megacities of southern and northern China

Study on fine aerosols composition can help understand the particles formation and is crucial for improving the accuracy of model simulations. Based on field data measured by a Q-ACSM (Quadrupole-Aerosol Chemical Speciation Monitor), we have comprehensively compared the characteristics, evolution, and potential formation mechanisms of the components in NR-PM2.5 during wintertime at two megacities (Beijing and Guangzhou) of southern and northern China. We show that as PM pollution intensifies, the mass fraction of the primary aerosols (e.g., COA, HOA) in PM2.5 in Guangzhou increased, along with a slight decline in proportion of both the secondary organic (SOA) and inorganic (SIA) aerosols; In contrast, in Beijing, the proportion of the SIA ramped up from 28 % to 53 % with the pollution evolution; and the fraction of SOA in total OA also increased due to a substantial increment in the proportion of MO-OOA (from 29 % to 48 %), suggesting a significance of the secondary processes in worsening aerosols pollution in Beijing. Our further analysis demonstrates a leading role of aqueous pathway in the secondary formation of aerosols at the Beijing site, presenting an exponential rising of SIA and SOA with the relative humidity (RH) increase. Compared to Beijing, however, we find that the photochemical oxidation other than aqueous process in Guangzhou plays a more critical role in those secondary aerosols formation. Combined with the Hysplit trajectory model, we identify the high humid conditions in Guangzhou are typically affected by clean marine air masses, explaining the slower response of secondary components to the RH changes. Moreover, the particles in Guangzhou were observed less hygroscopic that is adverse to the aerosol aqueous chemistry. The results provide basis for the precise control of PM pollution in different regions across China and would be helpful in improving model simulations.

Model Simulations and Predictions of Hydroxymethanesulfonate (HMS) in the Beijing-Tianjin-Hebei Region, China: Roles of Aqueous Aerosols and Atmospheric Acidity.

Hydroxymethanesulfonate (HMS) has been found to be an abundant organosulfur aerosol compound in the Beijing-Tianjin-Hebei (BTH) region with a measured maximum daily mean concentration of up to 10 μg per cubic meter in winter. However, the production medium of HMS in aerosols is controversial, and it is unknown whether chemical transport models are able to capture the variations of HMS during individual haze events. In this work, we modify the parametrization of HMS chemistry in the nested-grid GEOS-Chem chemical transport model, whose simulations provide a good account of the field measurements during winter haze episodes. We find the contribution of the aqueous aerosol pathway to total HMS is about 36% in winter in Beijing, due primarily to the enhancement effect of the ionic strength on the rate constants of the reaction between dissolved formaldehyde and sulfite. Our simulations suggest that the HMS-to-inorganic sulfate ratio will increase from the baseline of 7% to 13% in the near future, given the ambitious clean air and climate mitigation policies for the BTH region. The more rapid reductions in emissions of SO2 and NOx compared to NH3 alter the atmospheric acidity, which is a critical factor leading to the rising importance of HMS in particulate sulfur species.

Features of the reparative process after antiglaucoma surgery

Excessive fibrosis and scarring of newly created aqueous humor outflow pathways, mainly at the level of the intrascleral canal and filtering bleb, is a significant disadvantage of the so-called bleb-dependent antiglaucoma surgery. Taking into account the fact that aqueous humor, which flows evenly through the non-healing fistula under the hermetically sutured conjunctiva, is the forming substrate for the newly created outflow pathways, its composition also plays an important role in the body's response to surgical trauma. A large number of publications reliably demonstrate an increase in the concentration of various biologically active molecules in the aqueous humor of the anterior chamber of glaucoma patients. These are transforming growth factor β (TGF-β), vascular endothelial growth factor (VEGF), tumor necrosis factor-α (TNF-α), interleukins IL-6 and IL-8, etc., which concentration in cases of unsuccessful outcome of trabeculectomy was significantly increased compared to patients who underwent successful surgeries. In addition, it has been established that an imbalance of various matrix metalloproteinase pools, fibroblast activation, wound infiltration by neutrophils and macrophages, which in turn express a significant amount of pro-inflammatory cytokines and growth factors, contribute to the prolongation of inflammation and fibrosis. An important condition for the removal of aqueous humor from the filtering bleb area is the postoperative activation of conjunctival lymphatic angiogenesis, which suppression may be associated with prolonged inflammation or the active use of cytostatics. This literature review presents the complexities of the pathophysiological mechanisms of postoperative healing and the formation of newly created aqueous humor outflow pathways after antiglaucoma operations. At the same time, the question remains open about the effect of initial changes not only on the tissues of the ocular surface, but also in the aqueous humor of the anterior chamber, as well as the general condition of patients on the outcome of the operation.The purpose of this review is to present modern literature data on the pathophysiological mechanisms of the wound healing process and the features of postoperative healing regulation after antiglaucoma surgery.