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Experimental Cell Research Jul 2024Glaucoma is characterized by pathological elevation of intraocular pressure (IOP) due to dysfunctional trabecular meshwork (TM), which is the primary cause of...
Glaucoma is characterized by pathological elevation of intraocular pressure (IOP) due to dysfunctional trabecular meshwork (TM), which is the primary cause of irreversible vision loss. There are currently no effective treatment strategies for glaucoma. Mitochondrial function plays a crucial role in regulating IOP within the TM. In this study, primary TM cells treated with dexamethasone were used to simulate glaucomatous changes, showing abnormal cellular cytoskeleton, increased expression of extracellular matrix, and disrupted mitochondrial fusion and fission dynamics. Furthermore, glaucomatous TM cell line GTM3 exhibited impaired mitochondrial membrane potential and phagocytic function, accompanied by decreased oxidative respiratory levels as compared to normal TM cells iHTM. Mechanistically, lower NAD + levels in GTM3, possibly associated with increased expression of key enzymes CD38 and PARP1 related to NAD + consumption, were observed. Supplementation of NAD + restored mitochondrial function and cellular viability in GTM3 cells. Therefore, we propose that the aberrant mitochondrial function in glaucomatous TM cells may be attributed to increased NAD + consumption dependent on CD38 and PARP1, and NAD + supplementation could effectively ameliorate mitochondrial function and improve TM function, providing a novel alternative approach for glaucoma treatment.
Topics: Trabecular Meshwork; Mitochondria; Glaucoma; NAD; Humans; Membrane Potential, Mitochondrial; Intraocular Pressure; Cell Survival; ADP-ribosyl Cyclase 1; Cell Line; Poly (ADP-Ribose) Polymerase-1; Dexamethasone; Cells, Cultured
PubMed: 38897410
DOI: 10.1016/j.yexcr.2024.114137 -
Applied Clinical Informatics May 2024In times of omnipresent digitization and big data, telemedicine and electronic case files (ECFs) are gaining ground for networking between players in the health care...
BACKGROUND
In times of omnipresent digitization and big data, telemedicine and electronic case files (ECFs) are gaining ground for networking between players in the health care sector. In the context of the SALUS study, this approach is applied in practice in the form of electronic platforms to display and process disease-relevant data of glaucoma patients.
OBJECTIVES
The SALUS ECF is designed and implemented to support data acquisition and presentation, monitoring, and outcome control for patients suffering from glaucoma in a clinical setting. Its main aim is to provide a means for out- and inpatient exchange of information between various stakeholders with an intuitive user interface in ophthalmologic care. Instrument data, anamnestic data, and diagnostic assessments need to be accessible and historic data stored for patient monitoring. Quality control of the data is ensured by a reading center.
METHODS
Based on an intensive requirement analysis, we implemented the ECF as a web-based application in React with a Datomic back-end exposing REST and GraphQL APIs for data access and import. A flexible role management was developed, which addresses the various tasks of multiple stakeholders in the SALUS study. Data security is ensured by a comprehensive encryption concept. We evaluated the usability and efficiency of the ECF by measuring the durations medical doctors need to enter and work with the data.
RESULTS
The evaluation showed that the ECF is time-saving in comparison to paper-based assessments and offers supportive monitoring and outcome control for numerical and imaging-related data. By allowing patients and physicians to access the digital ECF, data connectivity as well as patient autonomy were enhanced.
CONCLUSION
ECFs have a great potential to efficiently support all patients and stakeholders involved in the care of glaucoma patients. They benefit from the efficient management and view of the data tailored to their specific role.
Topics: Glaucoma; Humans; Tonometry, Ocular; Self Care; Telemedicine; Electronic Health Records
PubMed: 38897231
DOI: 10.1055/s-0044-1787008 -
International Ophthalmology Jun 2024As the epidemiological and burden trends of glaucoma are changing, it is extremely necessary to re-investigate geographical differences and trends. Here we use data from...
PURPOSE
As the epidemiological and burden trends of glaucoma are changing, it is extremely necessary to re-investigate geographical differences and trends. Here we use data from the 2019 Global burden of Disease, which aims to report the prevalence and disability-adjusted life years of glaucoma injury to assess the latest epidemiological models and trends from 1990 to 2019.
METHOD
Annual case numbers, age-standardized rates of prevalence, DALYs, and their estimated annual percentage changes (EAPCs) for glaucoma between 1990 and 2019 were derived from the GBD 2019 study. The relationship between glaucoma disease burden and social demographic index (SDI) was also investigated in this study.
RESULTS
In 2019, there were 7.47 million prevalent cases and 0.75 million DALYs cases, which increased by 92.53% and 69.23% compared with 1990 respectively. The global age-standardized rate of prevalence (ASPR) and age-standardized rate of DALYs (ASDR) decreased during 1990-2019 (EAPC = - 0.55 and - 1, respectively). In 2019, the highest ASPR and ASDR of Glaucoma were all observed in Mali, whereas the lowest occurred in Taiwan (Province of China). In terms of gender, males were more likely to suffer from glaucoma than females, especially the elderly.
CONCLUSIONS
The global prevalence and DALYs of glaucoma had an absolute increase during the past 30 years. The disease burden caused by glaucoma is closely related to socioeconomic level, age, gender, and other factors, and these findings provide a basis for policymakers from the perspective of social management.
Topics: Humans; Global Burden of Disease; Glaucoma; Prevalence; Female; Male; Middle Aged; Aged; Adult; Global Health; Age Distribution; Disability-Adjusted Life Years; Sex Distribution; Quality-Adjusted Life Years; Adolescent; Aged, 80 and over; Young Adult; Child; Cost of Illness; Blindness
PubMed: 38896279
DOI: 10.1007/s10792-024-03222-6 -
F1000Research 2023The purpose of this study was to compare iCare HOME (TA022) with Goldmann applanation tonometer and to evaluate the self-tonometry measurements among the Indian...
The purpose of this study was to compare iCare HOME (TA022) with Goldmann applanation tonometer and to evaluate the self-tonometry measurements among the Indian population. Eligible patients underwent iCare HOME training through guided demonstration (verbal, pictorial, video) and practised self-tonometry measures using iCare HOME. Certification for independent iCare HOME measure was provided if first iCare HOME intraocular pressure (IOP) measurement fell within ± 5 mmHg of Goldmann applanation tonometer (GAT) measurement which was measured by the trained clinician (principal investigator). Certified participants underwent simulated home self-tonometry measurements using iCare HOME, and agreement with GAT IOP measurements was assessed. Seven of 83 participants (8.43%) failed to complete the study due to difficulty in performing the task, leading to non-certification. Patients who could use the iCare HOME had a mean age of 53 ± 15.55years (53% males; 46% females). Only one in 12 subjects did not qualify to use iCare HOME. The overall mean difference between iCare HOME and GAT was 0.83 mmHg (95%, 3.92 and -2.25). At various pressure ranges, 7-16 mmHg, 17-23 mmHg and >23 mmHg, the mean difference between iCare HOME and GAT was 1.22 mmHg (95%, 4.32 and -1.86), 0.77 mmHg (95%,3.69 and -2.19), -0.11 mmHg (95%, 2.52 and -2.74) respectively. The intra-class correlation coefficient of the iCare HOME device was 0.997(95% CI,0.995-0.998). Patients were able to perform self- tonometry using iCare HOME with good reliability and safety. iCare HOME can be used to address the issue of difficulty in acquiring frequent and diurnal IOP measurements by patients doing self-tonometry from home.
Topics: Humans; Male; Intraocular Pressure; Female; Glaucoma; Tonometry, Ocular; Middle Aged; Adult; Aged; Self Care
PubMed: 38894819
DOI: 10.12688/f1000research.123104.2 -
International Journal of Molecular... Jun 2024Although glaucoma is a leading cause of irreversible blindness worldwide, its pathogenesis is incompletely understood, and intraocular pressure (IOP) is the only...
Although glaucoma is a leading cause of irreversible blindness worldwide, its pathogenesis is incompletely understood, and intraocular pressure (IOP) is the only modifiable risk factor to target the disease. Several associations between the gut microbiome and glaucoma, including the IOP, have been suggested. There is growing evidence that interactions between microbes on the ocular surface, termed the ocular surface microbiome (OSM), and tear proteins, collectively called the tear proteome, may also play a role in ocular diseases such as glaucoma. This study aimed to find characteristic features of the OSM and tear proteins in patients with glaucoma. The whole-metagenome shotgun sequencing of 32 conjunctival swabs identified Actinobacteria, Firmicutes, and Proteobacteria as the dominant phyla in the cohort. The species was only found in healthy controls, and their conjunctival microbiomes may be enriched in genes of the phospholipase pathway compared to glaucoma patients. Despite these minor differences in the OSM, patients showed an enrichment of many tear proteins associated with the immune system compared to controls. In contrast to the OSM, this emphasizes the role of the proteome, with a potential involvement of immunological processes in glaucoma. These findings may contribute to the design of new therapeutic approaches targeting glaucoma and other associated diseases.
Topics: Humans; Glaucoma; Proteome; Male; Female; Microbiota; Tears; Middle Aged; Eye Proteins; Aged; Conjunctiva; Metagenome; Adult
PubMed: 38892444
DOI: 10.3390/ijms25116257 -
International Journal of Molecular... May 2024To analyze in vivo scleral changes induced by MicroPulse transscleral laser therapy (MP-TLT) in refractory glaucoma using anterior segment-optical coherence tomography...
To analyze in vivo scleral changes induced by MicroPulse transscleral laser therapy (MP-TLT) in refractory glaucoma using anterior segment-optical coherence tomography (AS-OCT). Forty-two candidate patients for MP-TLT were consecutively enrolled and underwent AS-OCT at baseline and after six months. MP-TLT success was defined as an intraocular pressure (IOP) reduction by one-third. The main outcome measures were the mean superior (S-), inferior (I-), and total (T-) intra-scleral hypo-reflective space area (MISHA: mm) and scleral reflectivity (S-SR, I-SR, T-SR; arbitrary scale) as in vivo biomarkers of uveoscleral aqueous humor (AH) outflow. The IOP was the secondary outcome. The relations between the baseline-to-six months differences (D) of DS-MISHA, DI-MISHA, and DT-MISHA and DS-SR, DI-SR, DT-SR, and DIOP, were investigated. At 6 months, the median IOP reduction was 21% in the failures and 38% in the successes. The baseline S-MISHA, I-MISHA, and T-MISHA did not differ between the groups, while S-SR and T-SR were higher in the successes ( < 0.05). At six months, successful and failed MP-TLTs showed a 50% increase in S-MISHA ( < 0.001; = 0.037), whereas I-SR and T-SR reduced only in the successes ( = 0.002; = 0.001). When comparing DS-MISHA, DI-MISHA, and DT-MISHA and DS-SR, DI-SR, and DT-SR, there were no significant differences between the groups. In the successful procedures, DIOP was positively correlated with DT-MISHA and DI-MISHA (ρ = 0.438 and ρ = 0.490; < 0.05). MP-TLT produced potentially advantageous modifications of the sclera in refractory glaucoma. Given the partial correlation between these modifications and post-treatment IOP reduction, our study confirmed that the activation of the uveoscleral AH outflow route could significantly contribute to the IOP lowering after MP-TLT.
Topics: Humans; Tomography, Optical Coherence; Sclera; Male; Female; Glaucoma; Middle Aged; Intraocular Pressure; Laser Therapy; Aged; Aqueous Humor; Uvea; Adult; Treatment Outcome
PubMed: 38892100
DOI: 10.3390/ijms25115913 -
International Journal of Molecular... May 2024Childhood glaucoma encompasses congenital and juvenile primary glaucoma, which are heterogeneous, uncommon, and irreversible optic neuropathies leading to visual...
Childhood glaucoma encompasses congenital and juvenile primary glaucoma, which are heterogeneous, uncommon, and irreversible optic neuropathies leading to visual impairment with a poorly understood genetic basis. Our goal was to identify gene variants associated with these glaucoma types by assessing the mutational burden in 76 matrix metalloproteinase-related genes. We studied 101 childhood glaucoma patients with no identified monogenic alterations using next-generation sequencing. Gene expression was assessed through immunohistochemistry. Functional analysis of selected gene variants was conducted in cultured cells and in zebrafish. Patients presented a higher proportion of rare variants in four metalloproteinase-related genes, including and , compared to controls. ADAMTSL4 protein expression was observed in the anterior segment of both the adult human and zebrafish larvae's eye, including tissues associated with glaucoma. In HEK-293T cells, expression of four ADAMTSL4 variants identified in this study showed that two variants (p.Arg774Trp and p.Arg98Trp) accumulated intracellularly, inducing endoplasmic reticulum stress. Additionally, overexpressing these ADAMTSL4 variants in zebrafish embryos confirmed partial loss-of-function effects for p.Ser719Leu and p.Arg1083His. Double heterozygous functional suppression of and zebrafish orthologs resulted in reduced volume of both the anterior eye chamber and lens within the chamber, supporting a genetic interaction between these genes. Our findings suggest that accumulation of partial functional defects in matrix metalloproteinase-related genes may contribute to increased susceptibility to early-onset glaucoma and provide further evidence supporting the notion of a complex genetic inheritance pattern underlying the disease.
Topics: Humans; Animals; Zebrafish; Glaucoma; Child; Male; Female; Child, Preschool; HEK293 Cells; Genetic Predisposition to Disease; Mutation; Matrix Metalloproteinases; ADAMTS Proteins; Adolescent; Infant; Zebrafish Proteins; Endoplasmic Reticulum Stress
PubMed: 38891949
DOI: 10.3390/ijms25115757 -
International Journal of Molecular... May 2024The ocular glymphatic system subserves the bidirectional polarized fluid transport in the optic nerve, whereby cerebrospinal fluid from the brain is directed along... (Review)
Review
The ocular glymphatic system subserves the bidirectional polarized fluid transport in the optic nerve, whereby cerebrospinal fluid from the brain is directed along periarterial spaces towards the eye, and fluid from the retina is directed along perivenous spaces following upon its axonal transport across the glial lamina. Fluid homeostasis and waste removal are vital for retinal function, making the ocular glymphatic fluid pathway a potential route for targeted manipulation to combat blinding ocular diseases such as age-related macular degeneration, diabetic retinopathy, and glaucoma. Several lines of work investigating the bidirectional ocular glymphatic transport with varying methodologies have developed diverging mechanistic models, which has created some confusion about how ocular glymphatic transport should be defined. In this review, we provide a comprehensive summary of the current understanding of the ocular glymphatic system, aiming to address misconceptions and foster a cohesive understanding of the topic.
Topics: Humans; Glymphatic System; Animals; Optic Nerve; Retina; Eye; Glaucoma
PubMed: 38891923
DOI: 10.3390/ijms25115734 -
International Journal of Molecular... May 2024Glaucoma is a chronic neurodegenerative disease that poses a significant threat of irreversible blindness worldwide. Current treatments for glaucoma focus on reducing... (Review)
Review
Glaucoma is a chronic neurodegenerative disease that poses a significant threat of irreversible blindness worldwide. Current treatments for glaucoma focus on reducing intraocular pressure (IOP), which is the only modifiable risk factor. Traditional anti-glaucomatous agents, including carbonic anhydrase inhibitors, beta-blockers, alpha-2 agonists, and prostaglandin analogs, work by either improving uveoscleral outflow or reducing aqueous humor production. Rho kinase (ROCK) inhibitors represent a novel class of anti-glaucomatous drugs that have emerged from bench to bedside in the past decade, offering multifunctional characteristics. Unlike conventional medications, ROCK inhibitors directly target the trabecular meshwork outflow pathway. This review aims to discuss the mechanism of ROCK inhibitors in reducing IOP, providing neuroprotection, and preventing fibrosis. We also highlight recent studies and clinical trials evaluating the efficacy and safety of ROCK inhibitors, compare them with other clinical anti-glaucomatous medications, and outline future prospects for ROCK inhibitors in glaucoma treatment.
Topics: Humans; Glaucoma; rho-Associated Kinases; Protein Kinase Inhibitors; Intraocular Pressure; Animals
PubMed: 38891764
DOI: 10.3390/ijms25115576 -
Handbook of Experimental Pharmacology Jun 2024Hypertension is a very prevalent condition associated with high mortality and morbidity, secondary to changes resulting in blood vessels and resultant end-organ damage....
Hypertension is a very prevalent condition associated with high mortality and morbidity, secondary to changes resulting in blood vessels and resultant end-organ damage. Haemodynamic changes, including an initial rise in cardiac output followed by an increase in total peripheral resistance, denote the early changes associated with borderline or stage 1 hypertension, especially in young men. Increased sodium reabsorption leading to kidney damage is another mechanism proposed as one of the initial triggers for essential hypertension. The underlying pathophysiological mechanisms include catecholamine-induced α- and ß-adrenoceptor stimulation, and renin-angiotensin-aldosterone system activation leading to endothelial dysfunction which is believed to lead to persistent blood pressure elevation.α blockers, α agonists, and ß blockers were among the first oral anti-hypertensives. They are no longer first-line therapy after outcome trials did not demonstrate any benefits over and above other agents, despite similar blood pressure reductions. Angiotensin-converting enzyme inhibitors (or angiotensin receptor blockers), calcium channel blockers, and thiazide-like diuretics are now considered the first line of therapy, although adrenoceptor agents still have a role as second- or third-line therapy. The chapter also highlights hypertension in specific medical conditions such as pregnancy, phaeochromocytoma, hyperthyroidism, portal hypertension, pulmonary arterial hypertension, and ocular hypertension, to provide an overview for clinicians and researchers interested in the role of adrenoceptors in the pathophysiology and management of hypertension.
PubMed: 38890192
DOI: 10.1007/164_2024_719