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Frontiers in Bioengineering and... 2024Glaucoma, the leading cause of irreversible blindness globally, affects more than 70 million people across the world. When initial treatments prove ineffective,...
Glaucoma, the leading cause of irreversible blindness globally, affects more than 70 million people across the world. When initial treatments prove ineffective, especially for cases with high intraocular pressure (IOP), the preferred approach involves employing glaucoma drainage devices (GDDs). This study introduces a novel self-adjustable glaucoma drainage device (SAGDD) designed to maintain IOP within the desired biological range (10 mmHg < IOP <18 mmHg) by dynamically modulating its fluidic resistance. Inspired by the starling resistor, we designed a circular valve with a thin, flexible membrane placed over the valve's inlet and outlet. To achieve the ideal design for the SAGDD and optimize its parameters, we utilized fluid-solid interaction (FSI) numerical models and conducted parametric studies, wherein simulations demonstrated the validity of the concept. Subsequently, to confirm and validate the numerical results, we fabricated a SAGDD at a 3:1 scale and subjected it to testing. Our findings demonstrate that, on a 3:1 scale, a circular SAGDD with a diameter of 8.1 mm and a stainless-steel membrane with a thickness of 10 µm effectively maintained IOP within the target range when the membrane exposed to external pressures of 7.5 or 10 mmHg. In summary, our study establishes a strong foundation for further exploration of the potential efficacy of SAGDD as a promising treatment for glaucoma. The cost-effectiveness and simplicity of its design, devoid of costly instrumentation, hold considerable promise in addressing the challenges associated with glaucoma.
PubMed: 38756411
DOI: 10.3389/fbioe.2024.1383459 -
Cell Communication and Signaling : CCS May 2024Diabetic retinopathy (DR) is a major cause of blindness and is characterized by dysfunction of the retinal microvasculature. Neutrophil stasis, resulting in retinal...
BACKGROUND
Diabetic retinopathy (DR) is a major cause of blindness and is characterized by dysfunction of the retinal microvasculature. Neutrophil stasis, resulting in retinal inflammation and the occlusion of retinal microvessels, is a key mechanism driving DR. These plugging neutrophils subsequently release neutrophil extracellular traps (NETs), which further disrupts the retinal vasculature. Nevertheless, the primary catalyst for NETs extrusion in the retinal microenvironment under diabetic conditions remains unidentified. In recent studies, cellular communication network factor 1 (CCN1) has emerged as a central molecule modulating inflammation in pathological settings. Additionally, our previous research has shed light on the pathogenic role of CCN1 in maintaining endothelial integrity. However, the precise role of CCN1 in microvascular occlusion and its potential interaction with neutrophils in diabetic retinopathy have not yet been investigated.
METHODS
We first examined the circulating level of CCN1 and NETs in our study cohort and analyzed related clinical parameters. To further evaluate the effects of CCN1 in vivo, we used recombinant CCN1 protein and CCN1 overexpression for gain-of-function, and CCN1 knockdown for loss-of-function by intravitreal injection in diabetic mice. The underlying mechanisms were further validated on human and mouse primary neutrophils and dHL60 cells.
RESULTS
We detected increases in CCN1 and neutrophil elastase in the plasma of DR patients and the retinas of diabetic mice. CCN1 gain-of-function in the retina resulted in neutrophil stasis, NETs extrusion, capillary degeneration, and retinal leakage. Pre-treatment with DNase I to reduce NETs effectively eliminated CCN1-induced retinal leakage. Notably, both CCN1 knockdown and DNase I treatment rescued the retinal leakage in the context of diabetes. In vitro, CCN1 promoted adherence, migration, and NETs extrusion of neutrophils.
CONCLUSION
In this study, we uncover that CCN1 contributed to retinal inflammation, vessel occlusion and leakage by recruiting neutrophils and triggering NETs extrusion under diabetic conditions. Notably, manipulating CCN1 was able to hold therapeutic promise for the treatment of diabetic retinopathy.
Topics: Diabetic Retinopathy; Extracellular Traps; Animals; Neutrophils; Humans; Cysteine-Rich Protein 61; Mice; Male; Mice, Inbred C57BL; Diabetes Mellitus, Experimental; Retina; Female; Middle Aged
PubMed: 38755602
DOI: 10.1186/s12964-024-01653-3 -
BMC Genomics May 2024Childhood glaucoma (CG) encompasses a heterogeneous group of genetic eye disorders that is responsible for approximately 5% of childhood blindness worldwide....
Childhood glaucoma (CG) encompasses a heterogeneous group of genetic eye disorders that is responsible for approximately 5% of childhood blindness worldwide. Understanding the molecular aetiology is key to improving diagnosis, prognosis and unlocking the potential for optimising clinical management. In this study, we investigated 86 CG cases from 78 unrelated families of diverse ethnic backgrounds, recruited into the Genomics England 100,000 Genomes Project (GE100KGP) rare disease cohort, to improve the genetic diagnostic yield. Using the Genomics England/Genomic Medicine Centres (GE/GMC) diagnostic pipeline, 13 unrelated families were solved (13/78, 17%). Further interrogation using an expanded gene panel yielded a molecular diagnosis in 7 more unrelated families (7/78, 9%). This analysis effectively raises the total number of solved CG families in the GE100KGP to 26% (20/78 families). Twenty-five percent (5/20) of the solved families had primary congenital glaucoma (PCG), while 75% (15/20) had secondary CG; 53% of this group had non-acquired ocular anomalies (including iris hypoplasia, megalocornea, ectopia pupillae, retinal dystrophy, and refractive errors) and 47% had non-acquired systemic diseases such as cardiac abnormalities, hearing impairment, and developmental delay. CYP1B1 was the most frequently implicated gene, accounting for 55% (11/20) of the solved families. We identified two novel likely pathogenic variants in the TEK gene, in addition to one novel pathogenic copy number variant (CNV) in FOXC1. Variants that passed undetected in the GE100KGP diagnostic pipeline were likely due to limitations of the tiering process, the use of smaller gene panels during analysis, and the prioritisation of coding SNVs and indels over larger structural variants, CNVs, and non-coding variants.
Topics: Humans; Glaucoma; Male; Female; Child; Child, Preschool; Cytochrome P-450 CYP1B1; Mutation; Infant; Genomics; Pedigree; Adolescent; Forkhead Transcription Factors
PubMed: 38755526
DOI: 10.1186/s12864-024-10353-8 -
Healthcare Informatics Research Apr 2024This study investigated the prevalence of ophthalmic diseases in Quang Tri and Thai Nguyen, Vietnam, utilizing a smartphone-based fundus imaging (SBFI) system.
OBJECTIVES
This study investigated the prevalence of ophthalmic diseases in Quang Tri and Thai Nguyen, Vietnam, utilizing a smartphone-based fundus imaging (SBFI) system.
METHODS
This cross-sectional study included nearly 10,000 patients who visited community health centers between July and August 2019. All participants underwent visual acuity testing and fundus imaging. We collected demographic data and medical histories, and fundus images were captured using the EYELIKE system. Data were compiled on an online platform, allowing clinicians from other regions to make diagnoses.
RESULTS
The study revealed significant variations in visual acuity and the prevalence of ophthalmic diseases between the two regions. Quang Tri had a higher proportion of individuals with good eyesight compared to Thai Nguyen. In Quang Tri, nearly 50% of the population had media haze, while in Thai Nguyen, about one-third of the population was affected. The prevalence of glaucomatous optic nerve and age-related macular degeneration was approximately 1% higher in Quang Tri than in Thai Nguyen. These findings provide valuable insights into the eye health status of these regions, indicating that eye health in Quang Tri was poorer than in Thai Nguyen.
CONCLUSIONS
The prevalence rates of ophthalmic conditions in this study were within the expected ranges compared to those in other Asian countries, though they were somewhat low. The SBFI method, being simpler and more efficient than the Rapid Assessment of Avoidable Blindness, offers a promising approach for measuring and estimating the prevalence of ophthalmic diseases.
PubMed: 38755107
DOI: 10.4258/hir.2024.30.2.162 -
Clinics (Sao Paulo, Brazil) May 2024This study aimed to describe the behavioral patterns of data on cataract surgery performed in the Brazilian public health system before, during, and after the COVID-19...
PURPOSE
This study aimed to describe the behavioral patterns of data on cataract surgery performed in the Brazilian public health system before, during, and after the COVID-19 outbreak and estimate the setbacks generated by the pandemic to guide public policies.
MATERIALS AND METHODS
This was an observational, longitudinal, and descriptive epidemiological study based on data retrieved from the public health system's databases of cataract surgeries performed each year and in each region from 2015 to 2022.
RESULT
In Brazil, compared with the average of the 5-years preceding the pandemic, a 23 % reduction in the number of cataract surgeries was observed in 2020, followed by a 21 % increase in 2021, compensating for the majority of patients that were not operated on. However, the worsening situation of blindness caused by cataracts due to the pandemic not be avoided in the Central-West region, where unrecovered cases continue to accumulate.
CONCLUSION
The COVID-19 pandemic did not worsen the situation of cataract blindness in Brazil due to the efficacy of the measures taken by the government in resuming elective surgeries. However, the auhtors recommend that the distribution of resources for cataract surgeries should consider regional discrepancies based on epidemiological data.
PubMed: 38754224
DOI: 10.1016/j.clinsp.2024.100380 -
Frontiers in Endocrinology 2024Diabetic retinopathy (DR) is a microvascular complication of diabetes, severely affecting patients' vision and even leading to blindness. The development of DR is...
BACKGROUND
Diabetic retinopathy (DR) is a microvascular complication of diabetes, severely affecting patients' vision and even leading to blindness. The development of DR is influenced by metabolic disturbance and genetic factors, including gene polymorphisms. The research aimed to uncover the causal relationships between blood metabolites and DR.
METHODS
The two-sample mendelian randomization (MR) analysis was employed to estimate the causality of blood metabolites on DR. The genetic variables for exposure were obtained from the genome-wide association study (GWAS) dataset of 486 blood metabolites, while the genetic predictors for outcomes including all-stage DR (All DR), non-proliferative DR (NPDR) and proliferative DR (PDR) were derived from the FinnGen database. The primary analysis employed inverse variance weighted (IVW) method, and supplementary analyses were performed using MR-Egger, weighted median (WM), simple mode and weighted mode methods. Additionally, MR-Egger intercept test, Cochran's test, and leave-one-out analysis were also conducted to guarantee the accuracy and robustness of the results. Subsequently, we replicated the MR analysis using three additional datasets from the FinnGen database and conducted a meta-analysis to determine blood metabolites associated with DR. Finally, reverse MR analysis and metabolic pathway analysis were performed.
RESULTS
The study identified 13 blood metabolites associated with All DR, 9 blood metabolites associated with NPDR and 12 blood metabolites associated with PDR. In summary, a total of 21 blood metabolites were identified as having potential causal relationships with DR. Additionally, we identified 4 metabolic pathways that are related to DR.
CONCLUSION
The research revealed a number of blood metabolites and metabolic pathways that are causally associated with DR, which holds significant importance for screening and prevention of DR. However, it is noteworthy that these causal relationships should be validated in larger cohorts and experiments.
Topics: Humans; Mendelian Randomization Analysis; Diabetic Retinopathy; Genome-Wide Association Study; Polymorphism, Single Nucleotide
PubMed: 38752182
DOI: 10.3389/fendo.2024.1383035 -
Journal of Translational Medicine May 2024Corneal injuries, often leading to severe vision loss or blindness, have traditionally been treated with the belief that limbal stem cells (LSCs) are essential for...
BACKGROUND
Corneal injuries, often leading to severe vision loss or blindness, have traditionally been treated with the belief that limbal stem cells (LSCs) are essential for repair and homeostasis, while central corneal epithelial cells (CCECs) were thought incapable of such repair. However, our research reveals that CCECs can fully heal and maintain the homeostasis of injured corneas in rats, even without LSCs. We discovered that CXCL14, under PAX6's influence, significantly boosts the stemness, proliferation, and migration of CCECs, facilitating corneal wound healing and homeostasis. This finding introduces CXCL14 as a promising new drug target for corneal injury treatment.
METHODS
To investigate the PAX6/CXCL14 regulatory axis's role in CCECs wound healing, we cultured human corneal epithelial cell lines with either increased or decreased expression of PAX6 and CXCL14 using adenovirus transfection in vitro. Techniques such as coimmunoprecipitation, chromatin immunoprecipitation, immunofluorescence staining, western blot, real-time PCR, cell colony formation, and cell cycle analysis were employed to validate the axis's function. In vivo, a rat corneal epithelial injury model was developed to further confirm the PAX6/CXCL14 axis's mechanism in repairing corneal damage and maintaining corneal homeostasis, as well as to assess the potential of CXCL14 protein as a therapeutic agent for corneal injuries.
RESULTS
Our study reveals that CCECs naturally express high levels of CXCL14, which is significantly upregulated by PAX6 following corneal damage. We identified SDC1 as CXCL14's receptor, whose engagement activates the NF-κB pathway to stimulate corneal repair by enhancing the stemness, proliferative, and migratory capacities of CCECs. Moreover, our research underscores CXCL14's therapeutic promise for corneal injuries, showing that recombinant CXCL14 effectively accelerates corneal healing in rat models.
CONCLUSION
CCECs play a critical and independent role in the repair of corneal injuries and the maintenance of corneal homeostasis, distinct from that of LSCs. The PAX6/CXCL14 regulatory axis is pivotal in this process. Additionally, our research demonstrates that the important function of CXCL14 in corneal repair endows it with the potential to be developed into a novel therapeutic agent for treating corneal injuries.
Topics: PAX6 Transcription Factor; Animals; Cell Proliferation; Corneal Injuries; Wound Healing; Humans; Chemokines, CXC; Epithelium, Corneal; Rats, Sprague-Dawley; Epithelial Cells; Rats; Cell Movement; Male; Cell Line
PubMed: 38750454
DOI: 10.1186/s12967-024-05270-z -
PloS One 2024In nature, animals must navigate to forage according to their sensory inputs. Different species use different sensory modalities to locate food efficiently. For...
In nature, animals must navigate to forage according to their sensory inputs. Different species use different sensory modalities to locate food efficiently. For teleosts, food emits visual, mechanical, chemical, and/or possibly weak-electrical signals, which can be detected by optic, auditory/lateral line, and olfactory/taste buds sensory systems. However, how fish respond to and use different sensory inputs when locating food, as well as the evolution of these sensory modalities, remain unclear. We examined the Mexican tetra, Astyanax mexicanus, which is composed of two different morphs: a sighted riverine (surface fish) and a blind cave morph (cavefish). Compared with surface fish, cavefish have enhanced non-visual sensory systems, including the mechanosensory lateral line system, chemical sensors comprising the olfactory system and taste buds, and the auditory system to help navigate toward food sources. We tested how visual, chemical, and mechanical stimuli evoke food-seeking behavior. In contrast to our expectations, both surface fish and cavefish did not follow a gradient of chemical stimulus (food extract) but used it as a cue for the ambient existence of food. Surface fish followed visual cues (red plastic beads and food pellets), but, in the dark, were likely to rely on mechanosensors-the lateral line and/or tactile sensor-as cavefish did. Our results indicate cavefish used a similar sensory modality to surface fish in the dark, while affinity levels to stimuli were higher in cavefish. In addition, cavefish evolved an extended circling strategy to forage, which may yield a higher chance to capture food by swimming-by the food multiple times instead of once through zigzag motion. In summary, we propose that ancestors of cavefish, similar to the modern surface fish, evolved extended food-seeking behaviors, including circling motion, to adapt to the dark.
Topics: Animals; Feeding Behavior; Characidae; Biological Evolution; Caves; Cues; Blindness
PubMed: 38748713
DOI: 10.1371/journal.pone.0300793 -
Frontiers in Psychiatry 2024Studies using observational measures often fail to meet statistical standards for both reliability and validity. The present study examined the psychometric properties...
Parent-child interactive behavior in a German sample of parents with and without a mental illness: model replication and adaption of the Coding Interactive Behavior system.
Studies using observational measures often fail to meet statistical standards for both reliability and validity. The present study examined the psychometric properties of the Coding Interactive Behavior (CIB) System within a German sample of parent-child dyads. The sample consisted of 149 parents with and without a mental illness and their children [n experimental group (EG) = 75, n control group (CG) = 74] who participated in the larger Children of Mentally Ill Parents at Risk Evaluation (COMPARE) study. The age of the children ranged from 3 to 12 years (M = 7.99, SD = 2.5). Exploratory factor analysis supported a five-factor model of the CIB with items describing 1) parental sensitivity/reciprocity, 2) parental intrusiveness, 3) child withdrawal, 4) child involvement, and 5) parent limit setting/child compliance. Compared to international samples, the model was reduced by two independent dyadic factors. Testing for predictive validity identified seven items with predictive power to differentiate parental group membership. The CIB factors did not seem to be sufficiently sensitive to illustrate differences in interaction within a sample of parents with various mental illnesses. To apply the CIB to the described sample or similar ones in the future, additional measurement instruments may be necessary.
PubMed: 38745780
DOI: 10.3389/fpsyt.2024.1266383 -
Clinical Ophthalmology (Auckland, N.Z.) 2024Understanding sociodemographic factors associated with poor visual outcomes in children with juvenile idiopathic arthritis-associated uveitis may help inform practice...
PURPOSE
Understanding sociodemographic factors associated with poor visual outcomes in children with juvenile idiopathic arthritis-associated uveitis may help inform practice patterns.
PATIENTS AND METHODS
Retrospective cohort study on patients <18 years old who were diagnosed with both juvenile idiopathic arthritis and uveitis based on International Classification of Diseases tenth edition codes in the Intelligent Research in Sight Registry through December 2020. Surgical history was extracted using current procedural terminology codes. The primary outcome was incidence of blindness (20/200 or worse) in at least one eye in association with sociodemographic factors. Secondary outcomes included cataract and glaucoma surgery following uveitis diagnosis. Hazard ratios were calculated using multivariable-adjusted Cox proportional hazards models.
RESULTS
Median age of juvenile idiopathic arthritis-associated uveitis diagnosis was 11 (Interquartile Range: 8 to 15). In the Cox models adjusting for sociodemographic and insurance factors, the hazard ratios of best corrected visual acuity 20/200 or worse were higher in males compared to females (HR 2.15; 95% CI: 1.45-3.18), in Black or African American patients compared to White patients (2.54; 1.44-4.48), and in Medicaid-insured patients compared to commercially-insured patients (2.23; 1.48-3.37).
CONCLUSION
Sociodemographic factors and insurance coverage were associated with varying levels of risk for poor visual outcomes in children with juvenile idiopathic arthritis-associated uveitis.
PubMed: 38741584
DOI: 10.2147/OPTH.S456252