Treatment Of Primary Open-angle Glaucoma Research Articles

Efficiency and safety of the fixed latanoprost/ dorzolamide combination in open-angle glaucoma hypotensive treatment

Purpose: to determine the efficacy and safety of fixed latanoprost/dorzolamide combination Dorzoprost in hypotensive treatment of primary open-angle glaucoma (POAG) patients previously treated with latanoprost.Material and methods. An observational study included 30 patients (37 eyes) with moderate and advanced POAG who had uncompensated elevated IOP receiving latanoprost monotherapy. During the screening visit, latanoprost was switched to Dorzoprost instilled once in the evening. The targets were IOP, visual acuity, MD and PSD perimetry indices, retinal nerve fiber layer thickness, minimum width of the neuroretinal rim, macula retinal nerve fiber layer thickness, and adverse events. The observation period lasted 12 weeks. IOP was measured at weeks 4 and 12.Results. After 4 weeks, a statistically significant decrease in IOP was noted, which remained stable at 12 weeks. The average additional IOP decrease of those treated with Dorzoprost was 17%. Statistically insignificant positive changes were registered in visual acuity, static perimetry and optical coherence tomography. By the end of the observation period, 6 cases revealed a decrease in the degree of conjunctival hyperemia, while all dry eye syndrome cases (5 patients) showed a decrease in the severity of the signs of the syndrome.Conclusion. Dorzoprost has a significant additive hypotensive effect and a favorable safety profile.

Additive Therapy for Advanced Stages of Glaucoma

Purpose of the study: to evaluate the efficacy and feasibility of using brimonidine 0.2 % in the additive therapy of patients with advanced stages of glaucoma. Materials and methods. There were 59 patients (77 eyes) with advanced stages of primary open-angle, glaucoma (POAG) aged 68 to 83 years in the study. Patients were randomized into 2 groups depending on the received antihypertensive therapy. The first group (I) included 32 people (41 eyes) who used a fixed combination of a prostaglandin analogue (APG) or a carbonic anhydrase inhibitor (CAI) with a beta-blocker (BB) for the treatment of POAG. The second group (II) consisted of 27 patients (36 eyes) who had the α2-adrenergic agonist brimonidine — S3 added to the previously available combination of APG or ICA with BB. The observation period was 6 months. Results. Application of brimonidine — SZ in the additive therapy of advanced stages of glaucoma led to an additional hypotensive effect. By the end of the observation period in the group of patients treated with brimonidine, intraocular pressure decreased by an additional 10 % from the initial level. A good hypotensive effect contributed to an increase in functional parameters. Analysis of the results of static automatic perimetry showed a positive trend in the mean deviation (MD) and standard deviation pattern (PSD), which may indicate a neuroprotective effect of the drug. All patients noted good tolerability of treatment. Throughout the observation period, patients maintained a high level of adherence and performance.

Case report: Double implantation of the iStent inject in a high myope

The iStent inject is an ab-interno trabecular microbypass stent used in the treatment of primary open-angle glaucoma. Intraoperative complications are uncommon. However, we present the first reported case of simultaneous double-stent implantation, occurring in a 62-year-old Chinese male with high myopia and normal-tension glaucoma. Following an initial implantation failure, upon a single activation of the injector, simultaneous penetration of both stents into the trabecular meshwork occurred. Surgeons should be aware of the risk of double-implantation in myopic eyes with altered scleral rigidity, particularly when the first device is already located distally in the hub of the injector.

Hydrus microstent for the treatment of primary open-angle glaucoma: overview of its safety and efficacy

ABSTRACT Introduction Minimally invasive glaucoma surgeries (MIGS) are now a consolidated reality in many surgical units. The Hydrus Microstent is one of several MIGS devices bypassing trabecular outflow and had excellent results over the years. This article aims to review the key features of the Hydrus Microstent in terms of design, efficacy, and safety. Areas covered The present review analyses the main characteristics of the device by evaluating the technical and physical details of its functioning. The evidence that supports a clinical decision summarizes the most influential clinical trials and the most accurate systematic reviews. Expert opinion The Hydrus device has been extensively studied regarding biocompatibility and outflow potential. The subsequent clinical studies have been well-built and proved that the device effectively reduces intraocular pressure (IOP) and the eyedrop load. The device covers almost a quarter of Schlemm’s canal circumference, offering at least two advantages: cannulating the Schlemm’s canal provides evidence that the device has been implanted correctly; covering a larger area potentially allows to target multiple collector channels or at least areas of active outflow. This scaffold may prove more effective in naïve patients or subjects who used antiglaucoma eyedrops for a limited period, as the prolonged use of hypotonic medications has been associated with the surgical failure of ab interno microhook trabeculotomy.

Specific features of impaired tolerance to antihypertensive treatment in patients with primary open-angle glaucoma and a hereditary history of the disease

This review considers possible reasons for the decrease in the effectiveness of antihypertensive treatment in primary open-angle glaucoma (POAG) patients with a family history of the disease, presents clinical practice examples of the effectiveness and duration of antiglaucoma topical therapy and the mechanisms and manifestations of tachyphylaxis and tolerance disorders in such patients. Clinical features and the nature of POAG progression in patients with a hereditary predisposition may be reflected in the early decrease in the effectiveness of antihypertensive treatment. In some recent publications the authors proved a more aggressive course of POAG in patients with a family history of the disease, but despite that, such works at the moment are very limited in number and unsystematized. This, in turn, prevents drawing unambiguous conclusions regarding the features of the prescribed antihypertensive therapy. The article also discusses modern aspects of pharmacogenetics in patients with POAG, its further development will help minimize unwanted side effects as well as increase the effectiveness of antihypertensive drug treatment. The results of the work presented in this review allow systematization of the available data on impaired tolerance to antihypertensive therapy and maintain the need of further clinical research in this area.

Описательная статистика результатов комплексного лечения первичной открытоугольной глаукомы

В статье представлены результаты комплексного лечения первичной открытоугольной глаукомы, основанные на использовании дыхательных упражнений на фоне медикаментозного лечения. Данный метод показал свою высокую эффективность, которая проявилась в снижении и стабилизации истинного внутриглазного давления (Р0) на протяжении всего периода наблюдения (по Wilcoxon) в основной группе исследования и появлении статистически значимых различий с группой контроля через 6 месяцев комплексного лечения: в основной группе Р0 составило 17,30 (15,40–18,50), в группе контроля – 20,10 (18,80–23,80); также в стабилизации показателей поверхностного сосудистого сплетения в основной группе исследования, в то время как в группе контроля средняя плотность сосудистого рисунка постепенно уменьшалась, в первую очередь в парафовеолярной зоне: средняя плотность сосудов парафовеальной зоны макулы (inner) в начале наблюдения – 36,00 (34,70; 37,10), в конце исследования – 35,20 (34,10; 36,10) (Т=124,0; р<0,05); уплотнении показателей глубокого сосудистого сплетения, что проявилось в первую очередь в виде увеличения средней плотности сосудов в нижнем секторе макулы (total inferior) через 6 месяцев наблюдения (42,10 (41,70; 42,40)) и в конце исследования (42,20 (41,90; 42,70)) (Т=176,5; р<0,05), что позволило выявить статистически значимую разницу между группами в конце исследования по Mann – Whitney – U=387,5, р<0,05. Показатели радиального сосудистого сплетения также отреагировали на комплексное лечение, что проявилось в первую очередь в статистически значимом увеличении общей плотности сосудов перипапиллярной сетчатки (peripapillary) от начала наблюдения (40,90 (39,70; 41,60)) и через 12 месяцев (41,15 (40,60; 41,70)) (Т=180,0; р<0,05), это позволило выявить статистически значимую разницу между группами по Mann –Whitney в конце исследования – 41,15 (40,60; 41,70) в основной группе и 40,80 (39,90; 41,40) в группе контроля, р<0,05. Применение дыхательных упражнений по запатентованной авторами методике в комплексном лечении пациентов с первичной открытоугольной глаукомой позволяет эффективно снижать истинное внутриглазное давление, улучшать показатели гемодинамики глаз, что является важным, экономически обоснованным и доступным для широкого использования в клинической практике. The article presents the results of the complex treatment of primary open-angle glaucoma, based on the use of breathing exercises against the background of drug treatment. This method showed its high efficiency, which manifested itself in the reduction and stabilization of true intraocular pressure (P0) throughout the entire observation period (according to Wilcoxon) in the main study group and the appearance of statistically significant differences with the control group after 6 months of complex treatment: in the main group, P0 was 17.30 (15.40–18.50), in the control group – 20.10 (18.80–23.80); stabilization of the indicators of the superficial vascular plexus in the main study group, while in the control group the average density of the vascular pattern gradually decreased, primarily in the parafoveal zone: the average density of the vessels of the parafoveal zone of the macula (inner) at the beginning of the observation (36.00 (34.70; 37.10)) and at the end of the study (35.20 (34.10; 36.10)) (T=124.0; p<0.05); compaction of deep indicators, which manifested itself primarily in the form of compaction of the average density of vessels in the lower sector of the macula (total inferior) after 6 months of observation (42.10 (41.70; 42.40)) and at the end of the study (42.20 (41.90; 42.70)) (T=176.5; p<0.05), which made it possible to identify a statistically significant difference between the groups at the end of the study according to Mann-Whitney – U=387.5, p<0.05. The indicators of the radial vascular plexus also responded to complex treatment, which manifested itself primarily in a statistically significant increase in the total density of the vessels of the peripapillary retina (peripapillary) from the start of observation (40.90 (39.70; 41.60)) and after 12 months (41.15 (40.60; 41.70)) (T=180.0; p<0.05), which made it possible to identify a statistically significant difference between groups according to Mann-Whitney at the end of the study: 41.15 (40.60; 41.70) in the main group and 40.80 (39.90; 41.40) in the control group, p<0.05. The use of breathing exercises according to the method patented by the authors in the complex treatment of patients with primary open-angle glaucoma can effectively reduce the true intraocular pressure, improve eye hemodynamic parameters, which is important, economically feasible and available for widespread use in clinical practice.

Technological Advances in a Therapy of Primary Open-Angle Glaucoma: Insights into Current Nanotechnologies.

Glaucoma is a leading cause of irreversible blindness and is characterized by increased intraocular pressure (IOP) and progressive optic nerve damage. The current therapeutic approaches for glaucoma management, such as eye drops and oral medications, face challenges including poor bioavailability, low patient compliance, and limited efficacy. In recent years, nanotechnology has emerged as a promising approach to overcome these limitations and revolutionize glaucoma treatment. In this narrative review, we present an overview of the novel nanotechnologies employed in the treatment of primary open-angle glaucoma. Various nanosystems, including liposomes, niosomes, nanoparticles, and other nanostructured carriers, have been developed to enhance the delivery and bioavailability of antiglaucoma drugs. They offer advantages such as a high drug loading capacity, sustained release, improved corneal permeability, and targeted drug delivery to the ocular tissues. The application of nanotechnologies in glaucoma treatment represents a transformative approach that addresses the limitations of conventional therapies. However, further research is needed to optimize the formulations, evaluate long-term safety, and implement these nanotechnologies into clinical practice. With continued advancements in nanotechnology, the future holds great potential for improving the management and outcomes of glaucoma, ultimately preserving vision and improving the lives of millions affected by this debilitating disease.

Cytologic features of the bulbar conjunctiva in patients with primary open-angle glaucoma-associated dry eye disease

Purpose: To examine the features of the bulbar conjunctiva in patients who developed dry-eye disease (DED) after drug treatment for primary open-angle glaucoma (POAG). Methods: Impression cytology was performed by applying twice a strip of cellulose acetate filter to the ocular surface to remove the superficial epithelial layers of the temporal bulbar conjunctiva. The strips were removed with a peeling motion in a few seconds, and the samples were immediately fixed in 95% ethyl alcohol, stained with hematoxylin and eosin, mounted on glass slides and coverslipped for light microscopy. Squamous metaplasia was graded according to Nelson’s grading system on the basis of cell morphology, staining and integrity as well as the nucleus-to-cytoplasm ratio. This study included a case group of 80 patients (mean age, 63.8 +- 6.7 years) with POAG-associated DED, with the group being divided into four subgroups. Subgroups 1 and 2 were composed of 40 patients each, with glaucoma duration of less or more than 5 years, respectively. Subgroups a and b were composed of 40 patients each, with a number of topical ocular hypotensive drugs used equal to one or at least two, respectively. The control group was composed of 20 apparently healthy volunteers (mean age, 67.9 +- 8.9 years). All patients underwent a routine eye examination. Results: All patients with glaucoma had symptoms of DED with Ocular Surface Disease Index (OSDI) scores of at least 15. In subgroup 1, 60% had Nelson’s grade 1 and 40%, Nelson’s grade 2 squamous metaplasia. In subgroup 2, 10% had Nelson’s grade 1; 60%, Nelson’s grade 2 and 30%, Nelson’s grade 3 squamous metaplasia. In subgroup a, 20% had Nelson’s grade 1; 60%, Nelson’s grade 2 and 30%, Nelson’s grade 3 squamous metaplasia. In subgroup b, 10% had Nelson’s grade 1; 60%, Nelson’s grade 2 and 30%, Nelson’s grade 3 squamous metaplasia. Conclusion: Changes in the bulbar conjunctival epithelium corresponded to Nelson’s grade 2 or 3 squamous metaplasia in 80% of patients who developed DED after drug treatment for POAG. The severity of squamous metaplasia correlated with the duration of glaucoma and, consequently, longer use of hypotensive eye drops (r1 = 0.15, p1 = 0.02, p2 = 0.01). Findings of the current study and international guidelines argue for the use of the medications containing no preservatives or potentially toxic components in long-term therapy against glaucoma.

Long-Term Results of Combined Technology of Optimized YAG-Laser Trabeculostomy in the Treatment of Primary Open-Angle Glaucoma

Long-Term Results of Combined Technology of Optimized YAG-Laser Trabeculostomy in the Treatment of Primary Open-Angle Glaucoma

The potential for mitochondrial therapeutics in the treatment of primary open-angle glaucoma: a review.

Glaucoma, an age-related neurodegenerative disease, is characterized by the death of retinal ganglion cells (RGCs) and the corresponding loss of visual fields. This disease is the leading cause of irreversible blindness worldwide, making early diagnosis and effective treatment paramount. The pathophysiology of primary open-angle glaucoma (POAG), the most common form of the disease, remains poorly understood. Current available treatments, which target elevated intraocular pressure (IOP), are not effective at slowing disease progression in approximately 30% of patients. There is a great need to identify and study treatment options that target other disease mechanisms and aid in neuroprotection for POAG. Increasingly, the role of mitochondrial injury in the development of POAG has become an emphasized area of research interest. Disruption in the function of mitochondria has been linked to problems with neurodevelopment and systemic diseases. Recent studies have shown an association between RGC death and damage to the cells' mitochondria. In particular, oxidative stress and disrupted oxidative phosphorylation dynamics have been linked to increased susceptibility of RGC mitochondria to secondary mechanical injury. Several mitochondria-targeted treatments for POAG have been suggested, including physical exercise, diet and nutrition, antioxidant supplementation, stem cell therapy, hypoxia exposure, gene therapy, mitochondrial transplantation, and light therapy. Studies have shown that mitochondrial therapeutics may have the potential to slow the progression of POAG by protecting against mitochondrial decline associated with age, genetic susceptibility, and other pathology. Further, these therapeutics may potentially target already present neuronal damage and symptom manifestations. In this review, the authors outline potential mitochondria-targeted treatment strategies and discuss their utility for use in POAG.

How latanoprost changed glaucoma management.

Glaucoma is currently considered one of the leading causes of severe visual impairment and blindness worldwide. Topical medical therapy represents the treatment of choice for many glaucoma patients. Introduction of latanoprost, 25 years ago, with an entirely new mechanism of action from that of the antiglaucoma drugs used up to that time was a very important milestone. Since then, due mainly to their efficacy, limited systemic side effects and once daily dosing, prostaglandin analogues (PGAs) have become as the first-choice treatment for primary open-angle glaucoma. PGAs are in general terms well tolerated, although they are associated with several mild to moderate ocular and periocular adverse events. Among them, conjunctival hyperemia, eyelash changes, eyelid pigmentation, iris pigmentation and hypertrichosis around the eyes are the most prevalent. The objective of this paper is to review the role of PGAs in the treatment of glaucoma over the 25 years since the launch of Latanoprost and their impact on clinical practice outcomes.

Netarsudil monotherapy as the initial treatment for open-angle glaucoma and ocular hypertension in Indian patients: A real-world evaluation of efficacy and safety.

Glaucoma is the second leading cause of blindness worldwide, affecting more than 64 million people aged 40-80. The best way to manage primary open-angle glaucoma (POAG) is by lowering the intraocular pressure (IOP). Netarsudil is a Rho kinase inhibitor, the only class of antiglaucoma medications that reorganizes the extracellular matrix to improve the aqueous outflow through the trabecular pathway. An open-label, real-world, multicentric, observation-based 3-month study was performed for assessing the safety and ocular hypotensive efficacy of netarsudil ophthalmic solution (0.02% w/v) in patients with elevated IOP. Patients were given netarsudil ophthalmic solution (0.02% w/v) as a first-line therapy. Diurnal IOP measurements, best-corrected visual acuity, and adverse event assessments were recorded at each of the five visits (Day-1: screening day and first dosing day; subsequent observations were taken at 2 weeks, 4 weeks, 6 weeks, and 3 months). Four hundred and sixty-nine patients from 39 centers throughout India completed the study. The mean IOP at baseline of the affected eyes was 24.84 ± 6.39 mmHg (mean ± standard deviation). After the first dose, the IOP was measured after 2, 4, and 6 weeks, with the final measurement taken at 3 months. The percentage reduction in IOP in glaucoma patients after 3 months of once-daily netarsudil 0.02% w/v solution use was 33.34%. The adverse effects experienced by patients were not severe in the majority of cases. Some adverse effects observed were redness, irritation, itching, and others, but only a small number of patients experienced severe reactions, as reported in a decreasing order: redness > irritation > watering > itching > stinging > blurring. We found that netarsudil 0.02% w/v solution monotherapy when used as the first-line treatment in primary open-angle glaucoma and ocular hypertension was both safe and effective.

Микроимпульсная лазерная трабекулопластика как метод лечения первичной открытоугольной глаукомы

Purpose. Analysis of the results of treatment of primary open-angle glaucoma by the method of microimpulse laser trabeculoplasty with a power of 1000 mW and different operating cycles. Material and methods. 33 patients (36 eyes) who underwent microimpulse laser trabeculoplasty were included in the study: in the 1st month, MLT with a power of 1000 mW and a duty cycle of 15% was performed in 19 patients (21 eyes), in the 2nd month MLT s rabochim cyclom 10% 14 patients (15 glasses). Criterion of inclusion of development of patients with primary open glaucoma and pigmented angular anterior camera. Observation and measurement of VGD is carried out an hour after the laser procedure, after 10 days, and after 1; 3, 6 months. Results. In the MLT group with 15% duty cycle, at 6-month follow-up, we noted a decrease in IOP by more than 20% of baseline or more than 3 mmHg, in 78% of cases, however, in the MLT group with a 10% duty cycle, this figure was only 33%. Also, in the MLT group with 15% workers, there was a decrease in the number of antihypertensive drugs used by 32%, while in the MLT group with a 10% work cycle, this figure was 9%. Conclusions. Treatment with micropulse laser trabeculoplasty for primary open-angle glaucoma is a new method that affects pigmented cells without thermal damage. However, to achieve a hypotensive effect, the laser power should be 1000 mW, and the duty cycle is 15%, since with a duty cycle of 10%, no hypotensive effect is observed in the long-term observation period. Keywords: glaucoma, laser trabeculoplasty, pigmented anterior chamber angle

Novel potential drugs for the treatment of primary open-angle glaucoma using protein-protein interaction network analysis.

Glaucoma is the second leading cause of irreversible blindness, and primary open-angle glaucoma (POAG) is the most common type. Due to inadequate diagnosis, treatment is often not administered until symptoms occur. Hence, approaches enabling earlier prediction or diagnosis of POAG are necessary. We aimed to identify novel drugs for glaucoma through bioinformatics and network analysis. Data from 36 samples, obtained from the trabecular meshwork of healthy individuals and patients with POAG, were acquired from a dataset. Next, differentially expressed genes (DEGs) were identified to construct a protein-protein interaction (PPI) network. In both stages, the genes were enriched by studying the critical biological processes and pathways related to POAG. Finally, a drug-gene network was constructed, and novel drugs for POAG treatment were proposed. Genes with p < 0.01 and |log fold change| > 0.3 (1,350 genes) were considered DEGs and utilized to construct a PPI network. Enrichment analysis yielded several key pathways that were upregulated or downregulated. For example, extracellular matrix organization, the immune system, neutrophil degranulation, and cytokine signaling were upregulated among immune pathways, while signal transduction, the immune system, extracellular matrix organization, and receptor tyrosine kinase signaling were downregulated. Finally, novel drugs including metformin hydrochloride, ixazomib citrate, and cisplatin warrant further analysis of their potential roles in POAG treatment. The candidate drugs identified in this computational analysis require in vitro and in vivo validation to confirm their effectiveness in POAG treatment. This may pave the way for understanding life-threatening disorders such as cancer.

Evaluation of the efficacy and tolerability of 1% brinzolamide and 0.5% timolol fixed combination in the treatment of primary open-angle glaucoma

PURPOSE. To evaluate the effect of swtiching patients requiring a fixed combination of hypotensive eye drops from brinzolamide 1%/timolol 0.5% Azarga (Alcon Laboratories Inc, USA) to brinzolamide 1%/timolol 0.5% Brinarga (Sentiss Pharma, India), as well as to study the potential impact on tolerability and compliance, and compare the therapeutic effect of these two combinations.METHODS. Patients were switched from brinzolamide 1%/timolol 0.5% fixed combination eye drops Azarga to brinzolamide 1%/timolol 0.5% fixed combination eye drops Brinarga. In addition to the conventional instrumental examination methods, a questionnaire was used to identify potential side effects.RESULTS. Thirty-six patients (14 men and 22 women aged 41–89 years) were interviewed and examined in control appointments. A comparison of the severity and persistence of side effects of two types of fixed combination eye drops showed that brinzolamide 1%/timolol 0.5% (Brinarga) and brinzolamide 1%/timolol 0.5% (Azarga) can be considered as safe and effective conservative methods of glaucoma treatment.CONCLUSION. The fixed combination of brinzolamide 1%/timolol 0.5% (Brinarga) is comparable to brinzolamide 1%/timolol 0.5% (Azarga) in terms of the IOP reduction effectiveness. No pronounced adverse reactions were detected, which was comparable to the status before the change of therapy. Thus, the combination of brinzolamide 1%/timolol 0.5% (Brinarga) can be considered as an effective and safe treatment option for glaucoma patients.

Morphological and functional evaluation of oral nutritional supplements in primary open-angle glaucoma treatment—first results

Morphological and functional evaluation of oral nutritional supplements in primary open-angle glaucoma treatment—first results

Tadalafil to lower retinal venous pressure-anew approach to treatment of primary open-angle glaucoma?

Tadalafil to lower retinal venous pressure-anew approach to treatment of primary open-angle glaucoma?

Integrated aqueous humor ceRNA and miRNA-TF-mRNA network analysis reveals potential molecular mechanisms governing primary open-angle glaucoma pathogenesis.

To conduct an integrated bioinformatics analysis of extant aqueous humor (AH) gene expression datasets in order to identify key genes and the regulatory mechanism governing primary open-angle glaucoma (POAG) progression. Two datasets (GSE101727 and GSE105269) were downloaded from the Gene Expression Omnibus, and the messenger RNAs (mRNAs), microRNAs (miRNAs), and long noncoding RNAs (lncRNAs) were identified between controls and POAG patients. Differentially expressed (DE) mRNAs and DElncRNAs were then subjected to pathway enrichment analyses, after which a protein-protein interaction (PPI) network was generated. This network was then expanded to establish lncRNA-miRNA-mRNA and miRNA-transcription factor (TF)-mRNA networks. The GSE101727 dataset was used to identify 2746 DElncRNAs and 2208 DEmRNAs, while the GSE105269 dataset was used to identify 45 DEmiRNAs. We ultimately constructed a competing endogenous RNA (ceRNA) network incorporating 47 lncRNAs, six miRNAs, and 17 mRNAs. The proteins encoded by these 17 hub mRNAs were found to be significantly enriched for activities that may be linked to POAG pathogenesis. In addition, we generated a miRNA-TF-mRNA regulatory network containing two miRNAs (miR-135a-5p and miR-139-5p), five TFs (TGIF2, TCF3, FOS, and so on), and five mRNAs (SHISA7, ST6GAL2, TXNIP, and so on). The SHISA7, ST6GAL2, TXNIP, FOS, and DCBLD2 genes may be viable therapeutic targets for the prevention or treatment of POAG and are regulated by the TFs (TGIF2, HNF1A, TCF3, and FOS).

Metformin protects trabecular meshwork against oxidative injury via activating integrin/ROCK signals.

This study aimed to investigate the protective effect of metformin on trabecular meshwork (TM) and explore its molecular mechanisms in vivo and in vitro. Ocular hypertension (OHT) mouse models were induced with dexamethasone and further treated with metformin to determine the intraocular pressure (IOP)-lowering effect. Cultured human TM cells (HTMCs) were pre-stimulated with tert-butyl hydroperoxide (tBHP) to induce oxidative damage and then supplemented with metformin for another 24 hr. The expression of fibrotic markers and integrin/Rho-associated kinase (ROCK) signals, including α-smooth muscle actin (α-SMA), transforming growth factor-β (TGF-β), fibronectin, integrin beta 1, ROCK 1/2, AMP-activated protein kinase, myosin light chain 1, and F-actin were determined by western blotting and immunofluorescence. Reactive oxygen species (ROS) content was analysed using flow cytometry. Transmission electron microscopy was performed to observe microfilaments in HTMCs. It showed that metformin administration reduced the elevated IOP and alleviated the fibrotic activity of aqueous humour outflow in OHT models. Additionally, metformin rearranged the disordered cytoskeleton in the TM both in vivo and in vitro and significantly inhibited ROS production and activated integrin/ROCK signalling induced by tBHP in HTMCs. These results indicated that metformin reduced the elevated IOP in steroid-induced OHT mouse models and exerted its protective effects against oxidative injury by regulating cytoskeleton remodelling through the integrin/ROCK pathway. This study provides new insights into metformin use and preclinical evidence for the potential treatment of primary open-angle glaucoma.

IPSCs-Based Therapy for Trabecular Meshwork.

The trabecular meshwork (TM) of the eye serves as an essential tissue in controlling aqueous humor (AH) outflow and intraocular pressure (IOP) homeostasis. However, dysfunctional TM cells and/or decreased TM cellularity is become a critical pathogenic cause for primary open-angle glaucoma (POAG). Consequently, it is particularly valuable to investigate TM characteristics, which, in turn, facilitates the development of new treatments for POAG. Since 2006, the advancement in induced pluripotent stem cells (iPSCs) provides a new tool to (1) model the TM in vitro and (2) regenerate degenerative TM in POAG. In this context, we first summarize the current approaches to induce the differentiation of TM-like cells from iPSCs and compare iPSC-derived TM models to the conventional in vitro TM models. The efficacy of iPSC-derived TM cells for TM regeneration in POAG models is also discussed. Through these approaches, iPSCs are becoming essential tools in glaucoma modeling and for developing personalized treatments for TM regeneration.