Search

Background: Glaucoma is a leading cause of blindness strongly associated with psychiatric disorders, but the causal association between glaucoma and psychiatric disorders remains uncertain because of the susceptibility of observational studies to confounding and reverse causation. This study aims to explore the potential causal association between glaucoma and three highly related psychiatric disorders (Depression, Insomnia, and Schizophrenia) in the European and East Asian populations using a two-sample Mendelian randomization analysis. Methods: Instrumental variables (IVs) of depression, insomnia, and schizophrenia in the European population were obtained after strict filtering. Summary-level data for glaucoma and glaucoma subtypes (primary open-angle glaucoma and primary closed-angle glaucoma) were obtained as outcomes. The inverse variance weighting (IVW) method was used as the primary method. Additionally, the causal effect was evaluated in the East Asian population using the same methods to validate analysis results. The robustness of these results was confirmed using heterogeneity, pleiotropy, and Steiger directionality test. Results: The primary MR results indicated that genetically driven psychiatric disorders were not causally associated with glaucoma (Depression: odds ratio (OR): 1.15, 95% confidence interval (CI): 0.93-1.42, p = 0.20; Insomnia: OR: 1.14, 95% CI: 0.63-2.05, p = 0.66; Schizophrenia: OR: 1.00, 95% CI: 0.93-1.08, p = 0.95), either with the risk of glaucoma subtypes in the European population. Meanwhile, results in the East Asian population were consistent with the results among the European population (Depression: OR = 1.38, CI 0.75-2.53, p = 0.30; Insomnia: OR = 0.99, CI 0.83-1.18, p = 0.93; Schizophrenia: OR = 1.06, CI 0.94-1.20, p = 0.34) with similar causal estimates in direction. Consistency was obtained by corroborating with other supporting methods. Besides, the robustness of the results was proved and the directionality test confirmed our estimation of potential causal direction ( p < 0.001). Conclusion: This study found a non-causal association between psychiatric disorders and the risk of glaucoma in the European and East Asian populations, which contradicts many existing observational reports, indicating that increased psychiatric disorders in glaucoma patients were more likely modifiable rather not inheritable., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Fu, Feng, Liu, Lei and Kang.)

JOURNAL/nrgr/04.03/01300535-202503000-00033/figure1/v/2024-06-17T092413Z/r/image-tiff The organotypic retinal explant culture has been established for more than a decade and offers a range of unique advantages compared with in vivo experiments and cell cultures. However, the lack of systematic and continuous comparison between in vivo retinal development and the organotypic retinal explant culture makes this model controversial in postnatal retinal development studies. Thus, we aimed to verify the feasibility of using this model for postnatal retinal development studies by comparing it with the in vivo retina. In this study, we showed that postnatal retinal explants undergo normal development, and exhibit a consistent structure and timeline with retinas in vivo. Initially, we used SOX2 and PAX6 immunostaining to identify retinal progenitor cells. We then examined cell proliferation and migration by immunostaining with Ki-67 and doublecortin, respectively. Ki-67- and doublecortin-positive cells decreased in both in vivo and explants during postnatal retinogenesis, and exhibited a high degree of similarity in abundance and distribution between groups. Additionally, we used Ceh-10 homeodomain-containing homolog, glutamate-ammonia ligase (glutamine synthetase), neuronal nuclei, and ionized calcium-binding adapter molecule 1 immunostaining to examine the emergence of bipolar cells, Müller glia, mature neurons, and microglia, respectively. The timing and spatial patterns of the emergence of these cell types were remarkably consistent between in vivo and explant retinas. Our study showed that the organotypic retinal explant culture model had a high degree of consistency with the progression of in vivo early postnatal retina development. The findings confirm the accuracy and credibility of this model and support its use for long-term, systematic, and continuous observation., (Copyright © 2025 Copyright: © 2025 Neural Regeneration Research.)

Aberrant proliferation and migration of retinal pigment epithelium (RPE) cells contributes to the pathology of various ocular diseases. miR-27b has been reported to be crucial in the regulation of cell differentiation, proliferation, apoptosis, and migration. However, the role of miR-27b on RPE proliferation and migration remains largely unknown. Here the effect of miR-27b on ARPE-19 cells under platelet-derived growth factor (PDGF)-BB stimulation was explored. In this study, we found that the expression level of miR-27b was significantly reduced in ARPE-19 cells under PDGF-BB stimulation. Ectopic expression of miR-27b remarkably inhibited PDGF-BB-induced proliferation and migration in ARPE-19 cells. Furthermore, bioinformatic analysis and luciferase reporter assay showed that NADPH oxidase 2 (Nox2) was a direct target for miR-27b, and that knockdown of Nox2 expression mimicked the inhibitory effect of miR-27b on PDGF-BB -induced proliferation and migration in ARPE-19 cells, whereas, restoration of Nox2 expression showed an opposite effect. In addition, the ROS production and the activation of P13K/AKT/mTOR signaling induced by PDGF-BB were also suppressed by miR-27b overexpression or Nox2 silencing. Thus, these findings indicated that miR-27b exerted its protective role in RPE cells under PDGF-BB stimulation was partially through regulation of Nox2 and its downstream P13K/AKT/mTOR signaling, which might be a potential therapeutic approach for treatment of diseases caused by RPE proliferation, and migration., (Copyright © 2018. Published by Elsevier GmbH.)

Objective: To explore the effects of Gremlin on transdifferentiation and extracellular matrix synthesis in cultured human lens epithelium cells (HLEC)., Methods: This is an experimental research. HLEC were incubated with different concentrations of Gremlin (0, 100, 200 and 400 µg/L) for 24 h. The morphological changes of HLEC were observed by inverted microscope. Real-time PCR and Western-Blot were used to evaluate the expression of α-smooth muscle actin (α-SMA) (as a landmark protein of epithelial mesenchymal transition), fibronectin (Fn) and collagen type 1 (COL-1) (as major components of extracellular matrix) after stimulation with different time (0, 12, 24, 48, 72 h) by 200 µg/L Gremlin. The same parameters were observed in Gremlin. siRNA transfected HLEC which treated with 1.0 µg/L TGF-β2. α-SMA, Fn and COL-1 protein and mRNA expressions comparison with control group were analyzed using one-way and two-way ANOVA, while the difference between groups were compared using Turkey HSD and LSD-t test., Results: The normal morphology of HLEC showed polygonal and anchorage-dependent. After the incubation of different concentrations of Gremlin for 24 h, morphological feature of HLEC were changed from monolayer and polygonal to multilayer and spindle fibroblast-like cells, and the intercellular space widened. The expression of α-SMA, Fn and COL-1 were increased with prolonging of Gremlin treatment time (α-SMA gene induction: 1.00 ± 0.00, 1.62 ± 0.57, 3.40 ± 0.83, 5.90 ± 0.49, 7.97 ± 0.91; F = 61.64, P < 0.05, q = 6.43, 13.13, 18.66, P < 0.05; Fn gene induction: 1.00 ± 0.00, 3.26 ± 0.23, 5.86 ± 0.90, 10.17 ± 2.16, 12.89 ± 1.63; F = 42.03, P < 0.05, q = 6.45, 12.18, 15.79, P < 0.05; COL-1 gene induction: 1.00 ± 0.00, 1.78 ± 0.88, 6.80 ± 0.44, 12.76 ± 2.46, 21.12 ± 3.66; F = 51.79, P < 0.05, q = 4.97, 10.08, 17.26, P < 0.05) (α-SMA protein expression: 0.13 ± 0.02, 0.26 ± 0.02, 0.29 ± 0.09, 0.47 ± 0.06, 0.68 ± 0.05; F = 45.14, q = 5.11, 10.67, 17.40, P < 0.05; Fn protein expression: 0.16 ± 0.04, 0.26 ± 0.07, 0.65 ± 0.03, 0.82 ± 0.04, 0.73 ± 0.02; F = 144.4, q = 20.09, 26.78, 23.12, P < 0.05; COL-1 protein expression: 0.11 ± 0.02, 0.23 ± 0.09, 0.41 ± 0.05, 0.61 ± 0.03, 0.74 ± 0.03; F = 75.47, q = 9.99, 16.60, 21.07, P < 0.05). Gremlin. siRNA transfection effectively suppressed TGF-β2-induced expression of α-SMA, Fn, and COL-I (α-SMA gene induction: F = 81.89, P < 0.05, t = 3.234, 4.346, 10.35; t = 2.252, 7.272, 19.11, P < 0.05; Fn gene induction: F = 83.61, P < 0.05, t = 2.538, 8.202, 11.99; t = 6.316, 7.304, 14.80, P < 0.05; COL-1 gene induction: F = 73.64, P < 0.05, t = 3.385, 7.942, 11.64; t = 4.794, 9.006, 13.75, P < 0.05; Gremlin gene induction: F = 46.11, P < 0.05, t = 5.08, 7.24, 8.27; t = 6.27, 8.27, 12.14, P < 0.05) (α-SMA protein expression: F = 129.6, P < 0.05, t = 4.34, 4.85; 3.83, 4.34; 13.03, 14.82, P < 0.05; Fn protein expression: F = 26.18, P < 0.05, t = 5.68, 5.95; 3.10, 4.06; 4.19, 4.73, P < 0.05; COL-1 protein expression: F = 41.37, P < 0.05, t = 6.93, 5.51; 7.82, 6.93; 8.71, 7.64, P < 0.05; Gremlin protein expression: F = 59.52, P < 0.05, t = 2.24, 3.49; 5.74, 6.23; 6.98, 9.98, P < 0.05)., Conclusions: Gremlin could induce HLEC to express α-SMA, Fn and COL-1 in a time-dependent manner and promote transdifferentiation and extracellular matrix synthesis. Specifically silencing the expression of Gremlin could effectively block the TGF-β2-induced EMT and ECM synthesis in HLEC.

Glaucoma is a neurodegenerative disease characterized by elevated intraocular pressure (IOP), which causes retinal ischemia and progressive neuronal death. Retinal ischemia/reperfusion (RIR) injury is a common clinical condition representing the main cause of irreversible visual field defects in humans. The aim of this study was to investigate whether non-apoptotic forms of programmed cell death (PCD) have an effect on RIR injury in an experimental model that replicates features of acute hypertensive glaucoma and to explore the possible underlying mechanisms. The activation of autophagy was investigated in retinal ganglion cells (RGCs) following RIR in comparison with a control group, using immunofluorescence against microtubule-associated protein 1 light chain 3 (LC3). RIR injury increased LC3 expression in the cytoplasm of RGCs in the ganglion cell layer (GCL) 6 h after the insult, and the increased expression was sustained throughout the experimental period. Following RIR insult, the number of neurons in the GCL significantly decreased. Ultra-structural analyses showed that double- or multiple-membrane autophagosomes were markedly accumulated in the cytoplasm of RGCs following IOP elevation. Since there are no known markers for paraptosis, its identification was based on morphological criteria. Electron microscopy (EM) analysis revealed severe structural alterations associated with cytoplasmatic vacuolization within the 6 h after RIR injury and RGC death. EM also revealed that vacuoles were derived predominantly from the progressive swelling of the endoplasmic reticulum (ER) and/or mitochondria in RGCs after RIR injury. The results provide novel evidence implicating an important role of autophagy and paraptosis in the pathogenesis of RIR injury. Autophagy and paraptosis take place during developmental cell death in the nervous system as well as in certain cases of neurodegeneration. Therefore, targeting autophagy and paraptosis could have therapeutic potential for the prevention of glaucoma involving RIR injury.

Purpose: To investigate the transfer efficiency and transient expression of plasmid vector coding enhanced green fluorescent protein (EGFP)gene pEGFP-N1 which was transferred into primary cultured human fetal retinal progenitor cells. To build up a tracking method for study of retinal progenitor cells transplantation., Methods: pEGFP-N1 plasmid was amplified in E.coli, primary cultured human fetal retinal progenitor cells transferred with pEGFP-N1 by means of CaCl2. The transfer efficiency was evaluated by flow cytometry. Transient expression in vitro was observed by fluorescent microscope and laser scanning confocal microscope., Results: The transfer efficiency of pEGFP-N1 into primary cultured human fetal retinal progenitor cells could maximumly reach to 32.45% during 48 hours. There was obvious expression of pEGFP-N1 in vitro at 48th hour after transferring., Conclusion: pEGFP-N1 is an ideal transient expression vector for primary cultured human fetal retinal progenitor cells in vitro. It is a useful tracer for transplantation of retinal progenitor cells.