Downregulation of ATP8B2 to Assess Plasmalogen Distribution and Far1 Expression in Primary Trabecular Meshwork Cells.

The trabecular meshwork (TM) from primary open-angle glaucoma (POAG) cases has been found to contain decreased levels of intracellular plasmalogens. Plasmalogens are a subset of lipids involved in diverse cellular processes such as intracellular signaling, membrane asymmetry, and protein regulation. Proper plasmalogen biosynthesis is regulated by rate-limiting enzyme fatty acyl-CoA reductase (Far1). ATPase phospholipid transporting 8B2 (ATP8B2) is a type IV P-type ATPase responsible for the asymmetric distribution of plasmalogens between the intracellular and extracellular leaflets of the plasma membranes. Here we describe the methodology for extraction and culturing of TM cells from corneal tissue and subsequent downregulation of ATP8B2 using siRNA transfection. Further quantification and downstream effects of ATP8B2 gene knockdown will be analyzed utilizing immunoblotting techniques.

Genome-wide RNA sequencing of ocular fibroblasts from glaucomatous and normal eyes: Implications for glaucoma management.

Primary open angle glaucoma is a leading cause of visual impairment and blindness which is commonly treated with drugs or laser but may require surgery. Tenon's ocular fibroblasts are involved in wound-healing after glaucoma filtration surgery and may compromise a favourable outcome of glaucoma surgery by contributing to fibrosis. To investigate changes in gene expression and key pathways contributing to the glaucomatous state we performed genome-wide RNA sequencing. Human Tenon's ocular fibroblasts were cultured from normal and glaucomatous human donors undergoing eye surgery (n = 12). mRNA was extracted and RNA-Seq performed on the Illumina platform. Differentially expressed genes were identified using a bioinformatics pipeline consisting of FastQC, STAR, FeatureCounts and edgeR. Changes in biological functions and pathways were determined using Enrichr and clustered using Cytoscape. A total of 5817 genes were differentially expressed between Tenon's ocular fibroblasts from normal versus glaucomatous eyes. Enrichment analysis showed 787 significantly different biological functions and pathways which were clustered into 176 clusters. Tenon's ocular fibroblasts from glaucomatous eyes showed signs of fibrosis with fibroblast to myofibroblast transdifferentiation and associated changes in mitochondrial fission, remodeling of the extracellular matrix, proliferation, unfolded protein response, inflammation and apoptosis which may relate to the pathogenesis of glaucoma or the detrimental effects of topical glaucoma therapies. Altered gene expression in glaucomatous Tenon's ocular fibroblasts may contribute to an unfavourable outcome of glaucoma filtration surgery. This work presents a genome-wide transcriptome of glaucomatous versus normal Tenon's ocular fibroblasts which may identify genes or pathways of therapeutic value to improve surgical outcomes.

The TGFß Induced MicroRNAome of the Trabecular Meshwork.

Primary open-angle glaucoma (POAG) is a progressive optic neuropathy with a complex, multifactorial aetiology. Raised intraocular pressure (IOP) is the most important clinically modifiable risk factor for POAG. All current pharmacological agents target aqueous humour dynamics to lower IOP. Newer therapeutic agents are required as some patients with POAG show a limited therapeutic response or develop ocular and systemic side effects to topical medication. Elevated IOP in POAG results from cellular and molecular changes in the trabecular meshwork driven by increased levels of transforming growth factor ß (TGFß) in the anterior segment of the eye. Understanding how TGFß affects both the structural and functional changes in the outflow pathway and IOP is required to develop new glaucoma therapies that target the molecular pathology in the trabecular meshwork. In this study, we evaluated the effects of TGF-ß1 and -ß2 treatment on miRNA expression in cultured human primary trabecular meshwork cells. Our findings are presented in terms of specific miRNAs (miRNA-centric), but given miRNAs work in networks to control cellular pathways and processes, a pathway-centric view of miRNA action is also reported. Evaluating TGFß-responsive miRNA expression in trabecular meshwork cells will further our understanding of the important pathways and changes involved in the pathogenesis of glaucoma and could lead to the development of miRNAs as new therapeutic modalities in glaucoma.

Corneal thickness and endothelial change after use of ocular hypotensive agents.

Corneal transplantation can restore visual function when visual impairment is caused by a corneal disease. However, this treatment is associated with the scarcity of cornea donors. The suitability of corneal donation from patients with glaucoma using ocular hypotensive agents (OHAs) is controversial. This study aimed to elucidate changes in corneal thickness, corneal endothelial cell density, and corneal endothelial cell hexagonality after OHA use in patients with primary open-angle glaucoma. We retrospectively reviewed the data of 53 glaucoma suspect eyes without OHA use and 106 primary open-angle glaucoma eyes under OHA use. All participants underwent corneal parameter assessment using SP-3000P (Topcon Corp., Tokyo, Japan) at the time of diagnosis and the final visit. The OHA dose and timing of use were recorded. The ocular hypotensive agents score (OHAS) was determined based on the number, formula, frequency, and duration of OHA use. Baseline data showed no significant differences between the two groups with and without OHA use. At the final visit, the OHA-treated group showed significantly lower corneal thickness and corneal endothelial cell density than those of the control group. A weak positive correlation between the OHAS and changes in corneal endothelial cell hexagonality was noted. However, no correlation was observed between the OHAS and changes in corneal thickness or endothelial cell density. In conclusion, patients with glaucoma and using OHAs should undergo the corneal structural properties examinations before donation to ensure the quality of donor cornea.

Silibinin attenuates TGF-ß2-induced fibrogenic changes in human trabecular meshwork cells by targeting JAK2/STAT3 and PI3K/AKT signaling pathways.

Transforming growth factor-ß2 (TGF-ß2) induced fibrogenic changes in human trabecular meshwork (HTM) cells have been implicated in trabecular meshwork (TM) damage and intraocular pressure (IOP) elevation in primary open-angle glaucoma (POAG) patients. Silibinin (SIL) exhibited anti-fibrotic properties in various organs and tissues. This study aimed to assess the effects of SIL on the TGF-ß2-treated HTM cells and to elucidate the underlying mechanisms. Our study found that SIL effectively inhibited HTM cell proliferation, attenuated TGF-ß2-induced cell migration, and mitigated TGF-ß2-induced reorganization of both actin and vimentin filaments. Moreover, SIL suppressed the expressions of fibronectin (FN), collagen type I alpha 1 chain (COL1A1), and alpha-smooth muscle actin (α-SMA) in the TGF-ß2-treated HTM cells. RNA sequencing indicated that SIL interfered with the phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB, also known as AKT) signaling pathway, extracellular matrix (ECM)-receptor interaction, and focal adhesion in the TGF-ß2-treated HTM cells. Western blotting demonstrated SIL inhibited the activation of Janus kinase 2 (JAK2)/signal transducers and activators of transcription 3 (STAT3) and the downstream PI3K/AKT signaling pathways induced by TGF-ß2, potentially contributing to its inhibitory effects on ECM protein production in the TGF-ß2-treated HTM cells. Our study demonstrated the ability of SIL to inhibit TGF-ß2-induced fibrogenic changes in HTM cells. SIL could be a potential IOP-lowering agent by reducing the fibrotic changes in the TM tissue of POAG patients, which warrants further investigation through additional animal and clinical studies.

SDPR expression in human trabecular meshwork and its potential role in racial disparities of glaucoma.

In order to identify how differential gene expression in the trabecular meshwork (TM) contributes to racial disparities of caveolar protein expression, TM dysfunction and development of primary open angle glaucoma (POAG), RNA sequencing was performed to compare TM tissue obtained from White and Black POAG surgical (trabeculectomy) specimens. Healthy donor TM tissue from White and Black donors was analyzed by PCR, qPCR, immunohistochemistry staining, and Western blot to evaluate SDPR (serum deprivation protein response; Cavin 2) and CAV1/CAV2 (Caveolin 1/Caveolin 2). Standard transmission electron microscopy (TEM) and immunogold labeled studies were performed. RNA sequencing demonstrated reduced SDPR expression in TM from Black vs White POAG patients' surgical specimens, with no significant expression differences in other caveolae-associated genes, confirmed by qPCR analysis. No racial differences in SDPR gene expression were noted in healthy donor tissue by PCR analysis, but there was greater expression as compared to specimens from patients with glaucoma. Analysis of SDPR protein expression confirmed specific expression in the TM regions, but not in adjacent tissues. TEM studies of TM specimens from healthy donors did not demonstrate any racial differences in caveolar morphology, but a significant reduction of caveolae with normal morphology and immuno-gold staining of SDPR were noted in glaucomatous TM as compared to TM from healthy donors. Linkage of SDPR expression levels in TM, POAG development, and caveolar ultrastructural morphology may provide the basis for a novel pathway of exploration of the pathologic mechanisms of glaucoma. Differential gene expression of SDPR in TM from Black vs White subjects with glaucoma may further our understanding of the important public health implications of the racial disparities of this blinding disease.

Tear metabolomics for the diagnosis of primary open-angle glaucoma.

Primary Open-Angle Glaucoma (POAG) is the most prevalent glaucoma type, and the leading cause of irreversible visual impairment and blindness worldwide. Identification of early POAG biomarkers is of enormous value, as there is not an effective treatment for the glaucomatous optic nerve degeneration (OND). In this pilot study, a metabolomic analysis, by using proton (1H) nuclear magnetic resonance (NMR) spectroscopy was conducted in tears, in order to determine the changes of specific metabolites in the initial glaucoma eyes and to discover potential diagnostic biomarkers. A classification model, based on the metabolomic fingerprint in tears was generated as a non-invasive tool to support the preclinical and clinical POAG diagnosis. 1H NMR spectra were acquired from 30 tear samples corresponding to the POAG group (n = 11) and the control group (n = 19). Data were analysed by multivariate statistics (partial least squares-discriminant analysis: PLS-DA) to determine a model capable of differentiating between groups. The whole data set was split into calibration (65%)/validation (35%), to test the performance and the ability for glaucoma discrimination. The calculated PLS-DA model showed an area under the curve (AUC) of 1, as well as a sensitivity of 100% and a specificity of 83.3% to distinguish POAG group versus control group tear data. This model included 11 metabolites, potential biomarkers of the disease. When comparing the study groups, a decrease in the tear concentration of phenylalanine, phenylacetate, leucine, n-acetylated compounds, formic acid, and uridine, was found in the POAG group. Moreover, an increase in the tear concentration of taurine, glycine, urea, glucose, and unsaturated fatty acids was observed in the POAG group. These results highlight the potential of tear metabolomics by 1H NMR spectroscopy as a non-invasive approach to support early POAG diagnosis and in order to prevent visual loss.

Reduced Thickness of the Retina in de novo Parkinson's Disease Shows A Distinct Pattern, Different from Glaucoma.

Background: Parkinson's disease (PD) patients experience visual symptoms and retinal degeneration. Studies using optical coherence tomography (OCT) have shown reduced thickness of the retina in PD, also a key characteristic of glaucoma. Objective: To identify the presence and pattern of retinal changes in de novo, treatment-naive PD patients compared to healthy controls (HC) and early primary open angle glaucoma (POAG) patients. Methods: Macular OCT data (10×10 mm) were collected from HC, PD, and early POAG patients, at the University Medical Center Groningen. Bayesian informative hypotheses statistical analyses were carried out comparing HC, PD-, and POAG patients, within each retinal cell layer. Results: In total 100 HC, 121 PD, and 78 POAG patients were included. We showed significant reduced thickness of the inner plexiform layer and retinal pigment epithelium in PD compared to HC. POAG patients presented with a significantly thinner retinal nerve fiber layer, ganglion cell layer, inner plexiform layer, outer plexiform layer, and outer photoreceptor and subretinal virtual space compared to PD. Only the outer segment layer and retinal pigment epithelium were significantly thinner in PD compared to POAG. Conclusions: De novo PD patients show reduced thickness of the retina compared to HC, especially of the inner plexiform layer, which differs significantly from POAG, showing a more extensive and widespread pattern of reduced thickness across layers. OCT is a useful tool to detect retinal changes in de novo PD, but its specificity versus other neurodegenerative disorders has to be established.

Genetic Basis of Pigment Dispersion Syndrome and Pigmentary Glaucoma: An Update and Functional Insights.

Pigment Dispersion Syndrome (PDS) and Pigmentary Glaucoma (PG) comprise a spectrum of ocular disorders characterized by iris pigment dispersion and trabecular meshwork changes, resulting in increased intraocular pressure and potential glaucomatous optic neuropathy. This review summarizes recent progress in PDS/PG genetics including rare pathogenic protein coding alterations (PMEL) and susceptibility loci identified from genome-wide association studies (GSAP and GRM5/TYR). Areas for future research are also identified, especially the development of efficient model systems. While substantial strides have been made in understanding the genetics of PDS/PG, our review identifies key gaps and outlines the future directions necessary for further advancing this important field of ocular genetics.

Direct observation and measurement of circumlental space and its relation to anterior chamber angle characteristics in iridotomized phakic eyes with primary angle closure disease.

Primary angle closure disease (PACD) is a major cause of blindness worldwide. It has a high prevalence in East Asia, especially in China, which leads to a higher incidence of blindness than open-angle glaucoma. The aim of this study was to directly observe the circumlental space (CLS) in laser peripheral iridotomized eyes with PACD and to determine whether this structure plays a role in the pathogenesis of PACD. Fifty eyes of 50 patients with PACD, who had received laser peripheral iridotomy performed with neodymium:yttrium-aluminum-garnet were recruited from glaucoma clinics from March 2021 to May 2022, including 17 primary angle closure suspect (PACS), 16 primary angle closure (PAC) and 17 primary angle closure glaucoma (PACG). They were classified into two groups based on whether the ciliary process and the crystalline lens equator were in contact using slit-lamp photograph: the attached group and the unattached group. The demographic, clinical characteristics and anterior segment parameters measured from ultrasound biomicroscopy were compared between the attached group and the unattached group. Thirty-three eyes were assigned to the attached group and 17 eyes belonged to the unattached group. In the unattached group, the mean CLS was 0.10 ± 0.07 mm. No significant differences were identified between the different diagnosis groups in age, sex, best-corrected visual acuity, intraocular pressure, white-to-white, axial length, central corneal thickness, anterior chamber depth, flat keratometry, steep keratometry or iridotomy diameter (p > 0.05). The unattached group had shorter trabecular-ciliary process distance (p = 0.021) and larger ciliary process area (p = 0.001) compared with the attached group. Small CLS and its potential effect (partial ciliary block) might be considered as one of the mechanisms of PACD.

Causal relationships between Gut microbiota and primary open-angle Glaucoma: A Mendelian randomization and mediation analysis of Glaucoma endophenotypes.

Primary open-angle glaucoma (POAG) is a widespread condition responsible for irreversible blindness, and its prevalence is expected to increase substantially in the coming decades. Despite its significance, the exact cause of POAG remains elusive, necessitating a comprehensive exploration of its pathogenesis. Emerging research suggests a potential link between alterations in gut microbiota composition and POAG. However, establishing causality in these associations remains a challenge. In this study, we employed Mendelian randomization (MR) analysis to investigate the potential causal relationships between gut microbiota (GM) and POAG. Significant bacteria taxa were further analyzed with POAG endophenotypes. We utilized data from genome-wide association studies (GWAS) for GM and POAG, as well as for glaucoma endophenotypes, including intraocular pressure (IOP), retinal nerve fiber layer (RNFL) thickness, vertical cup-to-disc ratio (VCDR), and central corneal thickness (CCT). Univariable, multivariable MR and mediation effect analysis were conducted. Our analysis revealed that certain taxa, including phylum Euryarchaeota, genus Odoribacter, Rumnicoccaceae UCG009, Ruminiclostridium9, unknown genus id.2071, and Eubacterium rectale group, were associated with an increased risk of POAG. On the other hand, family Victivallaceae, Lacchnospiraceae, genus Lachnoclostridium, Oscillospira, Ruminococcaceae UCG011, Alloprevotella, and Faecalibacterium were found to be associated with a decreased risk of POAG. Furthermore, some of these taxa were found to be connected to glaucoma endophenotypes. Through further multivariable MR analysis, it was determined that IOP, VCDR, and CCT might played mediating roles between GM and POAG. In conclusion, this study utilizes MR analysis to elucidate potential causal associations between GM and POAG, providing insights into specific GM taxa that influence POAG risk and related endophenotypes. These findings emphasize the potential role of the gut microbiota in the pathogenesis of POAG and pave the way for future research and therapeutic interventions.

Influence of choroidal microvasculature dropout on progressive retinal nerve fibre layer thinning in primary open-angle glaucoma: comparison of parapapillary ß-zones and γ-zones.

BACKGROUND/AIMS: To compare the influence of choroidal microvasculature dropout (cMvD) on progressive retinal nerve fibre layer (RNFL) thinning in glaucomatous eyes with parapapillary ß-zones and γ-zones. METHODS: 294 eyes with primary open-angle glaucoma (POAG) and parapapillary atrophy (PPA) underwent optical coherence tomography (OCT) to determine the type of PPA and OCT angiography scanning of the optic nerve head to determine the presence of cMvD. Eyes were classified based on the type of PPA (ß-zones and γ-zones), and their clinical characteristics were compared. Factors associated with the rate of rapid progressive RNFL thinning were determined in each group, including the presence of cMvD as an independent variable. RESULTS: Of the 294 eyes, 186 and 108 were classified as having ß-zones and γ-zones, respectively. The rate of RNFL thinning was slower (p<0.001), axial length was longer (p<0.001) and presence of cMvD was less frequent (57.4% vs 73.1%, p=0.006) in eyes with γ-zone than those with ß-zone. Multivariate analyses showed that greater lamina cribrosa curvature (p=0.047) and the presence of cMvD (p=0.010) were associated with a faster rate of RNFL thinning in eyes with ß-zone, whereas larger intraocular pressure fluctuation (p<0.001), shorter axial length (p=0.042) and greater baseline RNFL thickness (p<0.001) were associated with a faster rate of RNFL thinning in eyes with γ-zone. CONCLUSIONS: The presence of cMvD was significantly associated with a faster rate of RNFL thinning in POAG eyes with ß-zone, but not γ-zone. The pathogenic consequences of cMvD in POAG eyes may depend on accompanying peripapillary structures.

Relationship of Choroidal Microvasculature Dropout and Beta Zone Parapapillary Area With Visual Field Changes in Glaucoma.

PURPOSE: To evaluate the association between rates of choroidal microvasculature dropout (MvD) change, beta zone parapapillary atrophy (ß-PPA) area change, and visual field (VF) changes in eyes with primary open-angle glaucoma (POAG). DESIGN: Retrospective, observational cohort study. METHODS: In a tertiary glaucoma clinic, we included 76 eyes from 58 patients with POAG with and without localized MvD, who had ≥2 years of follow-up with a minimum of 4 visits with optical coherence tomography angiography and optical coherence tomography scans. ß-PPA area was evaluated using scanning laser ophthalmoscopy-like images and compared with the area of MvD on an en face choroidal vessel density map during the follow-up period. Joint longitudinal mixed effects models were used to estimate the rates of change in ß-PPA area or MvD area and VF mean deviation (MD). RESULTS: Mean rates of change in ß-PPA and MvD area were 0.037 mm2 (95% confidence interval [CI] 0.030-0.043 mm2) per year and 0.039 mm2 (95% CI 0.029-0.048 mm2) per year, respectively, over the mean follow-up of 4.1 years. In multivariable models, MvD area enlargement was significantly associated with faster rates of VF MD loss (0.03 mm2 [95% CI 0.02-0.04 mm2] per 1-dB worse, P < .001) but not ß-PPA area enlargement (0.04 mm2 [95% CI 0.03-0.05 mm2] per 1-dB worse, P = .252). CONCLUSION: MvD area rates, but not ß-PPA area rates, were associated with VF MD loss changes in eyes with POAG. Assessment of MvD is useful for the detection of patients with glaucoma who are at an increased risk of faster VF loss.

Relative Flow Index as a Novel Optical Coherence Tomography Angiography Biomarker in Primary Open Angle Glaucoma.

PRCIS: Relative flow indices as novel optical coherence tomography angiography (OCTA) biomarkers demonstrated reduced optic nerve head and peripapillary large vessel and capillary perfusion in primary open angle glaucoma (POAG). Large vessel perfusion correlated with disease severity and progression. PURPOSE: To introduce relative flow indices as novel OCTA biomarkers and their pathologic insights in POAG. MATERIALS AND METHODS: This is a retrospective case-control study where 57 POAG and 57 control eyes were included. OCTA 4.5×4.5 mm optic nerve head (ONH) were analyzed using ImageJ 1.53t to calculate global flow indices (GFIs) and relative flow indices (RFIs) for whole image optic nerve head, isolated radial peripapillary capillary plexus, and isolated large vessel angiograms. RESULTS: Retinal nerve fiber layer thickness (RNFLT), ONH vascular density (VD), except inside disc and large vessel VD, GFIs, and RFIs were lower in POAG than control. There was a positive correlation between RNFLT and both VD and GFIs. Among RFIs, only large vessel RFI (ONHLVRFI) demonstrated a positive correlation with average RNFLT. Linear regression demonstrated a significant positive coefficient for ONHLVRFI with RNFLT as the dependent variable. The area under receiver operating characteristic curve showed diagnostic accuracy ranging fair, good, and excellent for all biomarkers. Inferior RNFLT had the highest area under the curve (0.922) while optic nerve head large vessel density had the lowest (0.523). CONCLUSIONS: POAG showed structural loss of RNFL neurovascular unit manifesting as positively correlated reduction of VD and RNFLT. Also, POAG had lower global perfusion of the optic nerve head and peripapillary area, resulting in the positively correlated reduction of GFIs and RNFLT. Although RFIs were lower in POAG, only ONHLVRFI demonstrated a positive correlation and regression with RNFLT, implying that large vessel hypoperfusion was associated with POAG severity and progression.

Role of Glucocorticoids and Glucocorticoid Receptors in Glaucoma Pathogenesis.

The glucocorticoid receptor (GR), including both alternative spliced isoforms (GRα and GRß), has been implicated in the development of primary open-angle glaucoma (POAG) and iatrogenic glucocorticoid-induced glaucoma (GIG). POAG is the most common form of glaucoma, which is the leading cause of irreversible vision loss and blindness in the world. Glucocorticoids (GCs) are commonly used therapeutically for ocular and numerous other diseases/conditions. One serious side effect of prolonged GC therapy is the development of iatrogenic secondary ocular hypertension (OHT) and OAG (i.e., GC-induced glaucoma (GIG)) that clinically and pathologically mimics POAG. GC-induced OHT is caused by pathogenic damage to the trabecular meshwork (TM), a tissue involved in regulating aqueous humor outflow and intraocular pressure. TM cells derived from POAG eyes (GTM cells) have a lower expression of GRß, a dominant negative regulator of GC activity, compared to TM cells from age-matched control eyes. Therefore, GTM cells have a greater pathogenic response to GCs. Almost all POAG patients develop GC-OHT when treated with GCs, in contrast to a GC responder rate of 40% in the normal population. An increased expression of GRß can block GC-induced pathogenic changes in TM cells and reverse GC-OHT in mice. The endogenous expression of GRß in the TM may relate to differences in the development of GC-OHT in the normal population. A number of studies have suggested increased levels of endogenous cortisol in POAG patients as well as differences in cortisol metabolism, suggesting that GCs may be involved in the development of POAG. Additional studies are warranted to better understand the molecular mechanisms involved in POAG and GIG in order to develop new disease-modifying therapies to better treat these two sight threatening forms of glaucoma. The purpose of this timely review is to highlight the pathological and clinical features of GC-OHT and GIG, mechanisms responsible for GC responsiveness, potential therapeutic options, as well as to compare the similar features of GIG with POAG.

Optic nerve head vascular variations in pseudoexfoliative and primary open-angle glaucoma.

PURPOSE: The purpose of this study was to assess the optic nerve head microvascular changes in pseudoexfoliative and primary open-angle glaucoma and define the relationship between vessel density and retinal nerve fiber layer thickness. METHODS: This observational cross-sectional study assessed 72 eyes with primary open-angle glaucoma, 41 eyes with pseudoexfoliative glaucoma, and 60 healthy eyes. On the basis of optic nerve head-centered, 4.5 mm × 4.5 mm scan size images, we evaluated the vessel density, as well as the peripapillary sector, inside disk, and all sectoral quadrants. RESULTS: Both glaucoma Groups had lower vessel density in all regions compared with the healthy Group (p<0.05 for all variables). Vessel densities of the nasal inferior, inferior nasal, and inferior temporal sectors in both glaucoma Groups showed similar results (p=0.157, p=0.128, p=0.143, respectively). Eyes with pseudoexfoliative glaucoma had significantly lower vessel densities than eyes with primary open-angle glaucoma in all other regions (p<0.05 for all variables). For both glaucoma Groups, the average retinal nerve fiber layer thickness positively correlated with vessel density in all peripapillary sectors (p<0.05 for all variables). CONCLUSIONS: Reduction in vessel density correlated with the thinning of retinal nerve fiber layer in both glaucoma Groups. Decreased vessel density in the optic nerve head can be used to demonstrate the microvascular pathologies and possible ischemic changes that lead to faster progression and worse prognosis in pseudoexfoliative glaucoma.

[Features of neuropsychological status and results of magnetic resonance morphometry in patients with Alzheimer's disease and glaucoma]. / Osobennosti neiropsikhologicheskogo statusa i rezul'taty magnitno-rezonansnoi morfometrii u patsientov s bolezn'yu Al'tsgeimera i glaukomoi.

OBJECTIVE: To identify the relationship of neuropsychological changes in patients with Alzheimer's disease (AD) and primary open-angle glaucoma (POAG) and to evaluate the results of magnetic resonance (MR)-morphometry in patients with these diseases. MATERIAL AND METHODS: We examined 32 patients (median age 67 [61.25; 76.75] years, 78.1% women) diagnosed with AD and POAG. The patients were divided into the AD group (n=16) and the POAG group (n=16). Complaints and anamnesis were collected for all patients, neurological status and neuropsychological status were assessed. MRI of the brain, followed by morphometry, was performed. RESULTS: Cognitive impairments (CI) were revealed in patients of both groups. The severity of CI in patients with AD was more pronounced than in patients with POAG (p<0.001). Alzheimer's type of CI was detected in both groups. MR-morphometry revealed a decrease in the volume of the left hippocampus, the volume of the right and left amygdala as well as a decrease in the thickness of the right and left entorhinal cortex in the AD group compared with the POAG group (p<0.05). A significant decrease in the thickness of the right medial orbitofrontal cortex was found in the POAG group compared with the AD group (p<0.05). CONCLUSION: In AD and POAG, there is a similarity of the neuropsychological profile, which reflects the neurodegeneration characteristic of these diseases. MRI morphometry requires an assessment of both volumes and thickness of brain structures. A neuroimaging pattern identified in patients with POAG can be regarded as an indicator of the glaucomatous process.

Comparison of the Choroid in Primary Open Angle and Angle Closure Glaucoma Using Optical Coherence Tomography.

PRCIS: The current study highlights distinct choroidal alterations in primary open angle (POAG) and primary angle closure (PACG) glaucomas, underscoring the potential of the Choroidal Vascularity Index (CVI) as a valuable indicator for understanding glaucoma pathogenesis. PURPOSE: To evaluate choroidal structural changes in patients with POAG and PACG and healthy controls utilizing the CVI and subfoveal choroidal thickness by enhanced depth imaging optical coherence tomography. METHODS: This study was cross-sectional. A total of 171 eyes of 171 subjects, comprising 69 eyes with untreated POAG, 58 eyes with untreated PACG, and 44 healthy eyes, were enrolled in this study. Subfoveal choroidal thickness, luminal area (LA), stromal area (SA), and total choroidal area were measured on enhanced depth imaging-optical coherence tomography scans. The CVI parameter is calculated as the proportion of LA to the total choroidal area. RESULTS: This study included 69 patients with POAG with a mean age of 51.4 ± 13.3 years, 58 patients with PACG with a mean age of 57.0 ± 7.3 years, and 44 healthy subjects with a mean age of 51.11 ± 10.7 years. The CVI in the POAG and PACG groups was significantly lower than that in the control group ( P = 0.001 and P = 0.005, respectively); however, not significantly different between the two glaucoma groups ( P = 1.000). POAG eyes had significantly lower LA than PACG and controls ( P = 0.014 and P = 0.049, respectively), whereas PACG eyes had significantly greater SA than controls ( P = 0.041). CONCLUSIONS: The CVI of POAG and PACG eyes was significantly lower than that of normal eyes. A reduced LA was observed mainly in eyes with POAG, and an increased SA was observed mainly in eyes with PACG. The role of the choroid may differ between POAG and PACG eyes.

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.

Improved magnetic delivery of cells to the trabecular meshwork in mice.

Glaucoma is the leading cause of irreversible blindness worldwide and its most prevalent subtype is primary open angle glaucoma (POAG). One pathological change in POAG is loss of cells in the trabecular meshwork (TM), which is thought to contribute to ocular hypertension and has thus motivated development of cell-based therapies to refunctionalize the TM. TM cell therapy has shown promise in intraocular pressure (IOP) control, but existing cell delivery techniques suffer from poor delivery efficiency. We employed a novel magnetic delivery technique to reduce the unwanted side effects of off-target cell delivery. Mesenchymal stem cells (MSCs) were labeled with superparamagnetic iron oxide nanoparticles (SPIONs) and after intracameral injection were magnetically steered towards the TM using a focused magnetic apparatus ("point magnet"). This technique delivered the cells significantly closer to the TM at higher quantities and with more circumferential uniformity compared to either unlabeled cells or those delivered using a "ring magnet" technique. We conclude that our point magnet cell delivery technique can improve the efficiency of TM cell therapy and in doing so, potentially increase the therapeutic benefits and lower the risk of complications such as tumorigenicity and immunogenicity.