Inhibition of NLRP3 inflammasome by MCC950 under hypoxia alleviates photoreceptor apoptosis via inducing autophagy in Müller glia.

NLRP3 inflammasome activation has emerged as a critical initiator of inflammatory response in ischemic retinopathy. Here, we identified the effect of a potent, selective NLRP3 inhibitor, MCC950, on autophagy and apoptosis under hypoxia. Neonatal mice were exposed to hyperoxia for 5 days to establish oxygen-induced retinopathy (OIR) model. Intravitreal injection of MCC950 was given, and then autophagy and apoptosis markers were assessed. Retinal autophagy, apoptosis, and related pathways were evaluated by western blot, immunofluorescent labeling, transmission electron microscopy, and TUNEL assay. Autophagic activity in Müller glia after NLRP3 inflammasome inhibition, together with its influence on photoreceptor death, was studied using western blot, immunofluorescence staining, mRFP-GFP-LC3 adenovirus transfection, cell viability, proliferation, and apoptosis assays. Results showed that activation of NLRP3 inflammasome in Müller glia was detected in OIR model. MCC950 could improve impaired retinal autophagic flux and attenuate retinal apoptosis while it regulated the retinal AMPK/mTOR/ULK-1 pathway. Suppressed autophagy and depressed proliferation capacity resulting from hypoxia was promoted after MCC950 treatment in Müller glia. Inhibition of AMPK and ULK-1 pathway significantly interfered with the MCC950-induced autophagy activity, indicating MCC950 positively modulated autophagy through AMPK/mTOR/ULK-1 pathway in Müller cells. Furthermore, blockage of autophagy in Müller glia significantly induced apoptosis in the cocultured 661W photoreceptor cells, whereas MCC950 markedly preserved the density of photoreceptor cells. These findings substantiated the therapeutic potential of MCC950 against impaired autophagy and subsequent apoptosis under hypoxia. Such protective effect might involve the modulation of AMPK/mTOR/ULK-1 pathway. Targeting NLRP3 inflammasome in Müller glia could be beneficial for photoreceptor survival under hypoxic conditions.

MiR-146a reduces fibrosis after glaucoma filtration surgery in rats.

PURPOSE: To explore the impact of microRNA 146a (miR-146a) and the underlying mechanisms in profibrotic changes following glaucoma filtering surgery (GFS) in rats and stimulation by transforming growth factor (TGF)-ß1 in rat Tenon's capsule fibroblasts. METHODS: Cultured rat Tenon's capsule fibroblasts were treated with TGF-ß1 and analyzed with microarrays for mRNA profiling to validate miR-146a as the target. The Tenon's capsule fibroblasts were then respectively treated with lentivirus-mediated transfection of miR-146a mimic or inhibitor following TGF-ß1 stimulation in vitro, while GFS was performed in rat eyes with respective intraoperative administration of miR-146a, mitomycin C (MMC), or 5-fluorouracil (5-FU) in vivo. Profibrotic genes expression levels (fibronectin, collagen Iα, NF-KB, IL-1ß, TNF-α, SMAD4, and α-smooth muscle actin) were determined through qPCR, Western blotting, immunofluorescence staining and/or histochemical analysis in vitro and in vivo. SMAD4 targeting siRNA was further used to treat the fibroblasts in combination with miR-146a intervention to confirm its role in underlying mechanisms. RESULTS: Upregulation of miR-146a reduced the proliferation rate and profibrotic changes of rat Tenon's capsule fibroblasts induced by TGF-ß1 in vitro, and mitigated subconjunctival fibrosis to extend filtering blebs survival after GFS in vivo, where miR-146a decreased expression levels of NF-KB-SMAD4-related genes, such as fibronectin, collagen Iα, NF-KB, IL-1ß, TNF-α, SMAD4, and α-smooth muscle actin(α-SMA). Additionally, SMAD4 is a key target gene in the process of miR-146a inhibiting fibrosis. CONCLUSIONS: MiR-146a effectively reduced TGF-ß1-induced fibrosis in rat Tenon's capsule fibroblasts in vitro and in vivo, potentially through the NF-KB-SMAD4 signaling pathway. MiR-146a shows promise as a novel therapeutic target for preventing fibrosis and improving the success rate of GFS.

Aging, Cellular Senescence, and Glaucoma.

Aging is one of the most serious risk factors for glaucoma, and according to age-standardized prevalence, glaucoma is the second leading cause of legal blindness worldwide. Cellular senescence is a hallmark of aging that is defined by a stable exit from the cell cycle in response to cellular damage and stress. The potential mechanisms underlying glaucomatous cellular senescence include oxidative stress, DNA damage, mitochondrial dysfunction, defective autophagy/mitophagy, and epigenetic modifications. These phenotypes interact and generate a sufficiently stable network to maintain the cell senescent state. Senescent trabecular meshwork (TM) cells, retinal ganglion cells (RGCs) and vascular endothelial cells reportedly accumulate with age and stress and may contribute to glaucoma pathologies. Therapies targeting the suppression or elimination of senescent cells have been found to ameliorate RGC death and improve vision in glaucoma models, suggesting the pivotal role of cellular senescence in the pathophysiology of glaucoma. In this review, we explore the biological links between aging and glaucoma, specifically delving into cellular senescence. Moreover, we summarize the current data on cellular senescence in key target cells associated with the development and clinical phenotypes of glaucoma. Finally, we discuss the therapeutic potential of targeting cellular senescence for the management of glaucoma.

Inhibition of Ferroptosis Ameliorates Photoreceptor Degeneration in Experimental Diabetic Mice.

Diabetic retinopathy (DR) is a leading cause of vision impairment in the working-age population worldwide. Various modes of photoreceptor cell death contribute to the development of DR, including apoptosis and autophagy. However, whether ferroptosis is involved in the pathogenesis of photoreceptor degeneration in DR is still unclear. High-glucose (HG)-stimulated 661W cells and diabetic mice models were used for in vitro and in vivo experiments, respectively. The levels of intracellular iron, glutathione (GSH), reactive oxygen species (ROS), lipid peroxidation (MDA), and ferroptosis-related proteins (GPX4, SLC7A11, ACSL4, FTH1, and NCOA4) were quantified to indicate ferroptosis. The effect of ferroptosis inhibition was also assessed. Our data showed the levels of iron, ROS, and MDA were enhanced and GSH concentration was reduced in HG-induced 661W cells and diabetic retinas. The expression of GPX4 and SLC7A11 was downregulated, while the expression of ACSL4, FTH1, and NCOA4 was upregulated in the 661W cells cultured under HG conditions and in the photoreceptor cells in diabetic mice. Furthermore, the administration of the ferroptosis inhibitor ferrostatin-1 (Fer-1) obviously alleviated ferroptosis-related changes in HG-cultured 661W cells and in retinal photoreceptor cells in diabetic mice. Taken together, our findings suggest that ferroptosis is involved in photoreceptor degeneration in the development of the early stages of DR.

Robust adaptive three-dimensional trajectory tracking control scheme design for small fixed-wing UAVs.

This paper aims to tackle the three-dimensional trajectory tracking problems of small fixed-wing unmanned aerial vehicles subject to nonlinearities, uncertainties and wind disturbances via adaptive techniques. The control objective is to efficiently control the thrust and the deflections of control surfaces to ensure the unmanned aerial vehicle arrives at a specified location within a given time frame. However, achieving this goal for small fixed-wing unmanned aerial vehicles can be challenging because the precise dynamic model and several parameters are not accessible, making most existing control strategies unworkable. Motivated by these facts, based on feedback linearization techniques, we derive linear models with equivalent disturbances to describe the translational dynamics without requiring precise aerodynamic force model information. To deal with the dilemmas where the norm bounds of equivalent disturbances depend on control inputs, system states, and unknown disturbances, a novel robust adaptive control strategy is designed for position control. Based on the assumption of two-time separation, the control scheme incorporates two parts, namely, a position controller containing the horizontal-plane and altitude parts and a robust filter-based attitude regulator. Also, to prevent chattering issues, we design a practical and robust adaptive position controller under which the tracking error is ultimately bounded The overall closed-loop stability is theoretically investigated based on the Lyapunov arguments. Hardware-in-loop simulation experiments are performed to testify our developed control scheme.

Molecular signaling from microglia impacts macroglia autophagy and neurons survival in glaucoma.

Interactions between microglia and macroglia play important roles in the neurodegeneration of the central nervous system and so is the situation between microglia and Müller cells in retina neurodegenerations like glaucoma. This study focuses on the roles of microglia-derived osteopontin (OPN) in impacting Müller cells and retinal ganglion cells (RGCs). Rat model and cell pressurization culture were used to simulate glaucoma scenarios. Animals were differently treated with anti-OPN, suppressors of OPN receptors (Itgαvß3/CD44) or microglia inhibitor minocycline, while isolated retinal Müller cells were accordingly treated with conditioned media from microglia culture pretreated with pressuring, overexpression-OPN, SiR-OPN, or minocycline. SB203580 was introduced to explore the role of p38 MAPK signaling pathway. Results revealed microglia may secret OPN to impact Müller cells' autophagy and RGCs survival via binding to Itgαvß3/CD44 receptors in glaucomatous neurodegeneration with involvement of p38 MAPK pathway. This discovery may benefit understanding neurodegenerative disorders and exploring therapeutics.

Matrix Metalloproteinases in Glaucoma: An Updated Overview.

Matrix metalloproteinases (MMPs) are important regulators of the extracellular matrix (ECM) and are involved in many stages of cellular growth and development. An imbalance of MMP expression is also the basis of many diseases, including eye diseases, such as diabetic retinopathy (DR), glaucoma, dry eye, corneal ulcer, keratoconus. This paper describes the role of MMPs in the glaucoma and their role in the glaucomatous trabecular meshwork (TM), aqueous outflow channel, retina, and optic nerve (ON). This review also summarizes several treatments for glaucoma that target MMPs imbalance and suggests that MMPs may represent a viable therapeutic target for glaucoma.

Interleukin-17A modulates retinal inflammation by regulating microglial activation via the p38 MAPK pathway in experimental glaucoma neuropathy.

As a prototypical member of the IL-17 family, interleukin-17A (IL-17A) has received increasing attentions for its potent proinflammatory role as well as potential to be a key therapeutic target in human autoimmune inflammatory diseases; however, its roles in other pathological scenarios like neuroinflammations are not fully elucidated yet but appear essentially correlating and promising. Glaucoma is the leading cause of irreversible blindness with complicated pathogenesis still to be understood, where neuroinflammation was reported to be critically involved in its both initiation and progression. Whether IL-17A takes part in the pathogenesis of glaucoma through interfering neuroinflammation due to its potent proinflammatory effect is still unknown. In the present study, we investigated the role of IL-17A in the pathological process of glaucoma neuropathy as well as its relationship with the predominant immune inflammation mediator microglia in retina, trying to elucidate the underlying mechanisms from the view of inflammation modulation. In our study, RNA sequencing was performed for the retinas of chronic ocular hypertension (COH) and control mice. Western blot, RT-PCR, immunofluorescence, and ELISA were used to evaluate the microglial activation and proinflammatory cytokines release at conditioned levels of IL-17A, along with assessment of optic nerve integrity including retinal ganglion cells (RGCs) counting, axonal neurofilament quantification, and flash visual-evoked potential (F-VEP) examination. And the possibly involved signaling pathways were screened out to go through further validation in scenarios with conditioned IL-17A. Subsequently, IL-17A was found to be significantly upregulated in COH retina. Furthermore, suppression of IL-17A effectively diminished the loss of RGCs, improved axonal quality, and F-VEP performance in COH mice. Mechanistically, IL-17A promoted microglial activation and proinflammatory cytokines release along with enhanced phenotypic conversion of activated microglia to M2-type in early stage and to M1-type in late stage in glaucomatous retinas. Microglia elimination decreased the proinflammatory factors secretion, enhanced the RGCs survival and axonal quality mediated by IL-17A. Furthermore, IL-17A-induced the overactivation of microglia in glaucomatous condition was alleviated after blocking the p38 MAPK pathway. Taken together, IL-17A is involved in the regulation of retinal immune response and RGCs cell death in experimental glaucoma by essentially promoting retinal microglial activation via p38 MAPK signaling pathway. IL-17A dynamically regulates the phenotypic conversion of retinal microglia in experimental glaucoma partly depending on the duration of elevated intraocular pressure. Suppression of IL-17A contributes to alleviate glaucoma neuropathy and exhibits promising potential as an innovative target for therapeutic strategy in glaucoma.

Choroidal Microvasculature Dropout in Glaucoma.

Glaucoma is a group of diseases characterized by distinctive visual field defect and optic nerve atrophy usually associated with elevated intraocular pressure (IOP). It is one of the most serious visual disorders and the leading cause of irreversible blindness worldwide. As a multifactorial disease, the pathogenesis of glaucoma is complicated and has been far from fully understood, where vascular factors are recognized to play an important role in its development and progression of glaucoma. Empirical researches have shown that parapapillary choroidal microvasculature dropout (CMvD) is closely associated with the impairment of optic nerve head (ONH) perfusion, probably accelerating the progression of glaucoma. Accordingly, it is necessary to explore the details regarding the relationship between CMvD and glaucoma progress, hoping to enhance the understanding of pathogenesis of glaucoma. In this review, we aimed to establish comprehensive understanding of the relationship between CMvD and glaucoma with generally going through relevant up-to-date literatures. Among the events that are closely associated with CMvD, we summarized the ones specifically involved in the term of glaucomatous pathological process, including thickness of retinal nerve fiber layer (RNFL) thickness, lamina cribrosa (LC) morphology, cricumpapillary vessel density (cpVD) and visual function such as visual field (VF) defect as well as the prognosis of glaucoma. Although researchers have made great advances, there are still many issues need to be addressed particularly concerning the pathogenic role of CMvD in glaucoma development and its clinical implications with respect to glaucoma prognosis.

miR-124-3p regulates the proliferation and differentiation of retinal progenitor cells through SEPT10.

Retinal degenerative diseases such as glaucoma, retinitis pigmentosa, and age-related macular degeneration pose serious threats to human visual health due to lack of effective therapeutic approaches. In recent years, the transplantation of retinal progenitor cells (RPCs) has shown increasing promise in the treatment of these diseases; however, the application of RPC transplantation is limited by both their poor proliferation and their differentiation capabilities. Previous studies have shown that microRNAs (miRNA) act as essential mediators in the fate determination of stem/progenitor cells. In this study, we hypothesized that miR-124-3p plays a regulatory role in the fate of RPC determination by targeting Septin10 (SEPT10) in vitro. We observed that the overexpression of miR124-3p downregulates SEPT10 expression in RPCs, leading to reduced RPC proliferation and increased differentiation, specifically towards both neurons and ganglion cells. Conversely, antisense knockdown of miR-124-3p was shown to boost SEPT10 expression, enhance RPC proliferation, and attenuate differentiation. Moreover, overexpression of SEPT10 rescued miR-124-3p-caused proliferation deficiency while weakening the enhancement of miR-124-3p-induced-RPC differentiation. Results from this study show that miR-124-3p regulates RPC proliferation and differentiation by targeting SEPT10. Furthermore, our findings enable a more comprehensive understanding into the mechanisms of proliferation and differentiation of RPC fate determination. Ultimately, this study may be useful for helping researchers and clinicians to develop more promising and effective approaches to optimize the use of RPCs in treating retinal degeneration diseases.

Establishment of a minimally invasive distal traumatic optic neuropathy model in mice to investigate cascade reactions of retinal glial cells.

Traumatic optic neuropathy (TON) is a complication of craniocerebral, orbital and facial injuries, leading to irreversible vision loss. At present, there is no reliable, widely used animal model, although it has been confirmed that TON can cause the loss of retinal ganglion cells (RGC). However, the cascade reaction of retinal glial cells underlying TON is unclear. Therefore, the establishment of an animal model to explore the pathological mechanism of TON would be of great interest to the scientific community. In this study, we propose a novel mouse model utilizing a 3D stereotaxic apparatus combined with a 27G needle to evaluate damage to the optic nerve by micro-CT, anatomy, SD-OCT and F-VEP. Immunofluorescence, western blotting, qPCR experiments were conducted to investigate the loss of RGCs and activation or inactivation of microglia, astrocytes and Müller glial cells in the retina from the first week to the fourth week after modeling. The results showed that this minimally invasive method caused damage to the distal optic nerve and loss of RGC after optic nerve injury. Microglia cells were found to be activated from the first week to the third week; however, they were inactivated at the fourth week; astrocytes were activated at the second week of injury, while Müller glial cells were gradually inactivated following injury. In conclusion, this method can be used as a novel animal model of distal TON, that results in a series of cascade reactions of retinal glial cells, which will provide a basis for future studies aimed at exploring the mechanism of TON and the search for effective treatment methods.

Clinical Efficacy of Preoperative and Intraoperative Intravitreal Ranibizumab as Adjuvant Therapy of Ahmed Glaucoma Valve Implantation Combined with Vitrectomy in the Management of Neovascular Glaucoma with Diabetic Vitreous Hemorrhage.

Neovascular glaucoma (NVG) secondary to proliferative diabetic retinopathy (PDR) is a devastating ocular disease with poor prognosis. Intravitreal ranibizumab injection (IVR) has been used as adjuvant therapy of surgical interventions preoperatively or intraoperatively. This study aimed to determine the efficacy and safety of combined IVR as adjuvant therapy in treating NVG with vitreous hemorrhage (VH) in PDR. A total of 39 NVG patients with VH (39 eyes) received IVR 3 to 5 days before surgery, and then they were assigned to either pars plana vitrectomy (PPV) + Ahmed glaucoma valve (AGV) implantation (Group 1, n = 22) or PPV + AGV implantation + intraoperative IVR (Group 2, n = 17). Patients were followed up for at least 9 months. Intraocular pressure (IOP), anti-glaucoma medications, best corrected visual acuity (BCVA), surgical success rates and postoperative complications were compared. Results showed that IOP decreased promptly after surgery and was notably maintained at a mid-term follow-up in both groups, and no significant differences were observed (all p > 0.05). Additional intraoperative IVR significantly reduced postoperative recurrent VH and iris neovascularization (p = 0.047, p = 0.025, respectively). There was no remarkable difference in postoperative anti-glaucoma medications, BCVA and complications between two groups (all p > 0.05). In conclusion, preoperative and intraoperative IVR as adjuvant therapy of AGV implantation combined with PPV could be a safe and effective treatment for NVG with VH in PDR. An additional intraoperative anti-VEGF injection could significantly reduce postoperative VH and iris neovascularization.

Hydrogen sulfide supplement preserves mitochondrial function of retinal ganglion cell in a rat glaucoma model.

Glaucoma is a neurodegenerative disease of visual system characterized by gradual loss of retinal ganglion cells (RGC). Since mitochondrial dysfunction of RGC is significantly involved in the pathological mechanisms of glaucoma, and hydrogen sulfide (H2S) takes part in the pathogeny of glaucoma and shows promising potential in restoring mitochondrial function in other neurons, the authors aimed to investigate the impact of H2S on mitochondrial function of RGC with a rat glaucoma model. An established chronic ocular hypertension (COH) rat model induced by injection of cross-linking hydrogel into anterior chamber was adopted, and a H2S donor, sodium hydrosulfide (NaHS), was selected to treat rats through intraperitoneal injection. After a period of 4 weeks, RGCs were isolated from the subjected rats with an immunopanning method and went through evaluations of mitochondrial membrane potential (MMP), mitochondrial permeability transition pore (MPTP) opening, intracellular Ca2 + level, reactive oxygen species (ROS) level, and cytosolic Cytochrome C distribution. The results showed that the mitochondrial function of RGC in experimental glaucoma was markedly improved by H2S supplement, being presented as stabilization of MMP, alleviation of MPTP opening, improvement of intracellular Ca2+ hemostasis, reduction of ROS accumulation, and inhibition of Cytochrome C release. Our study implicated that preservation of mitochondrial function by H2S probably plays a key role in protecting RGC in the context of glaucomatous neuropathy, and it is worth further deepgoing research to benefit the development of glaucoma treatment.

Guarding a Subspace in High-Dimensional Space With Two Defenders and One Attacker.

This article considers a subspace guarding game in high-dimensional space which consists of a play subspace and a target subspace. Two faster defenders as a team cooperate to protect the target subspace by capturing an attacker which strives to enter the target subspace from the play subspace without being captured. A closed-form solution is provided from the perspectives of kind and degree. Contributions of the work include the use of the attack subspace (AS) method to construct the barrier, by which the game winner can be perfectly predicted before the game starts. In addition to this inclusion, with the priori information about the game result, a critical payoff function is designed when the defenders can win the game. Then, the optimal strategy for each player is explicitly reformulated as a saddle-point equilibrium. Finally, we apply these theoretical results to two half-space and half-plane guarding games in 3-D space and 2-D plane, respectively. Since the entire achieved developments are analytical, they require a little memory without the computational burden and allow for real-time updates, beyond the capacity of the traditional Hamilton-Jacobi-Isaacs method. It is worth noting that this is the first time in the current work to consider the target guarding games for arbitrary high-dimensional space and in a fully analytical form.

Quantitative evaluation of retinal and choroidal changes in Fabry disease using optical coherence tomography angiography.

To examine the retinal and choroidal changes in patients with Fabry disease (FD) using optical coherence tomography angiography (OCTA). FD patients and age- and sex-matched healthy subjects were enrolled. A detailed ophthalmological examination was performed for all participants. The retinal thickness, ganglion cell layer with inner plexiform layer (GCIPL) thickness, choroidal thickness (CT), vessel length density (VLD), vessel perfusion density (VPD), and foveal avascular zone (FAZ) were analyzed in a detailed way with OCTA. Moreover, all FD patients underwent several laboratory tests to evaluate systemic conditions. A total of 54 subjects comprising 26 FD patients and 28 normal controls were enrolled. The retinal thickness, GCIPL thickness, and FAZ area showed no significant differences between the two groups (all P > 0.05). Only the superior CT in FD patients was significantly thinner than that in the normal subjects (P = 0.040). The macular VLD and VPD in the FD group were significantly reduced compared with the healthy controls (P = 0.026, P = 0.008). The macular VLD in FD patients had no significant correlations with different laboratory results (all P > 0.05), while the macular VPD were negatively correlated with creatinine (r = - 0.432, P = 0.028) and cystatin C (r = - 0.422, P = 0.032). FD patients may have retinal vascular dropout and choroidal vascular alterations. Analysis of vessel density using OCTA might be useful in the clinical assessment in FD patients.

Isolation of microglia from retinas of chronic ocular hypertensive rats.

Microglia are the principal glial cells involved in the processes of immune inflammation within both retina and optic nerve, especially under the context of glaucomatous neuropathy. Considering the distinguishing role of retinal microglia in glaucoma and the lack of established protocol for microglia isolation from animal glaucoma model, the present study aimed to develop and validate a method with characteristics of both simplicity and efficiency for retinal microglia isolation from chronic ocular hypertensive (COH) rats. A Percoll gradient of various concentrations was used to separate microglia from whole retinal cells of the COH rats and control group. The finally isolated microglia were identified by CD11b and Iba-1 immunofluorescence staining, and the cell viability was determined by trypan blue staining. Additionally, the proportion of microglia in the whole retina cells was identified by flow cytometry. Results showed that the survival rates of isolated retinal microglia with the Percoll gradient method were 67.2 ± 4% and 67.6 ± 3% in control and COH groups, respectively. The proportion of the microglia population in the whole retinal cells was about 0.4-0.93%. To conclude, the present study confirmed that the application of Percoll gradient could effectively separate microglia from retinas of COH rats, which will probably enrich the tool kit for basic researchers of glaucoma specialty and help with scientific investigations.

Protective Effect of Total Panax Notoginseng Saponins on Retinal Ganglion Cells of an Optic Nerve Crush Injury Rat Model.

Irreversible loss of retinal ganglion cells (RGCs) is a common pathological feature of various optic nerve degenerative diseases such as glaucoma and ischemic optic neuropathy. Effective protection of RGCs is the key to successful treatment of these diseases. Total Panax notoginseng saponins (TPNS) are the main active component of Panax notoginseng, which has an inhibitory effect on the apoptosis pathway. This study is aimed at assessing the protective effect of TPNS on RGCs of the optic nerve crush (ONC) model of rats and exploring the underlying mechanisms. The intraperitoneal or intravitreal injection of TPNS was used based on the establishment of the rat ONC model. Fifteen days after the injury, the cell membrane fluorescent probe (Fluoro-Gold) was applied to retrograde RGCs through the superior colliculus and obtain the number of surviving RGCs. TUNEL assay was also used to detect the number and density of RGC apoptosis after the ONC model. The expression and distribution of Bcl-2/Bax, c-Jun/P-c-Jun, and P-JNK in the retina were demonstrated by Western blot analysis. After the intervention of TPNS, the rate of cell survival increased in different retinal regions (p < 0.05) and the number of apoptosis cells decreased. Regarding the expression of Bcl-2/Bax, c-Jun/P-c-Jun, and P-JNK-related apoptotic proteins, TPNS can reduce the level of apoptosis and play a role in protecting RGCs (p < 0.05). These findings indicate that topical administration of TPNS can inhibit cell apoptosis and promote RGC survival in the crushed optic nerve.

Demographic and prognostic factors of optic nerve astrocytoma: a retrospective study of surveillance, epidemiology, and end results (SEER).

BACKGROUND: Optic nerve astrocytomas (ONAs) are neurological neoplasms in the central nervous system (CNS), and they have the highest incidence rate among all the tumor types in the visual pathway. In this study, we conducted a Surveillance, Epidemiology, and End Results (SEER) -based research to explore the demographic, survival, and prognostic factors of patients diagnosed with ONAs. METHODS: Utilizing the SEER database, we retrospectively evaluated data of patients diagnosed with ONAs of all ages from 1984 to 2016. We used the Student's t distribution to test variables of patients and various characteristics, and Kaplan-Meier curve to illustrate overall survival (OS) with 95.0% confidence intervals (CIs). We also performed univariate and multivariate analyses to evaluate various variables' validity on overall survival. RESULTS: A total of 1004 cases were analyzed, and revealed that age (P<0.001, hazard ratio (HR) = 8.830, 95% CI: 4.088-19.073), tumor grade (P<0.001, HR = 1.927, 95% CI: 1.516-2.450), diagnostic confirmation (P<0.001, HR = 2.444, 95% CI: 1.632-3.660), and histology type (P = 0.046, HR = 1.563, 95% CI: 1.008-2.424) of the tumor were associated with decreased survival. CONCLUSIONS: From this large, comparative study of ONAs, we found that younger age may be considered as a protective indicator, while high-grade astrocytic tumors have a worse prognosis. We also found that diagnostic confirmation and tumor grade were independent prognostic factors in this patient population.

[Impacts of Anthropogenic Emission Reduction and Meteorological Conditions on PM2.5 Pollution in Typical Cities of Beijing-Tianjin-Hebei in Winter].

This study used sampling analysis and a CAMx-PSAT coupling model to analyze the components, transmission, and source apportionment of PM2.5 in Beijing and Tangshan in January 2018. The results showed that in January 2018, water-soluble inorganic ions (WSⅡs) accounted for 49.59% and 39.13% of PM2.5 mass concentrations in Beijing and Tangshan, respectively. The ratios of NO3- to SO42- were 2.02 and 1.51, respectively, indicating that pollution in both cities was dominated by mobile sources. In Beijing and Tangshan, PM2.5 accounted for 48.74% and 30.67% of transmission, respectively. Regional transmissions were mainly contributed by neighboring areas, northwest masses, and southwest masses. However, the contribution of the southwest passage to pollution in the respective cities increased by 9.65% and 15.02% during pollution periods. The principal sources contributing to PM2.5 pollution in Beijing were mobile and dust sources. Secondary ions were more obviously affected by regional contributions, mobile and industrial sources had the most significant effect in Tangshan, and most particulate matter and sulfate were contributed by local emissions. From 2013 to 2018, the dominant component of WSⅡs changed from sulfate to nitrate while the main pollution sources changed from coal-fired and industrial sources to mobile and dust sources. Meanwhile, in January 2018, the meteorological factors were more favorable for pollution mitigation than in 2013. The meteorological impact of secondary ions is closely related to the lower relative humidity in 2018, compared to 2013.

Corrigendum: Evaluation of the Effectiveness of a Chronic Ocular Hypertension Mouse Model Induced by Intracameral Injection of Cross-Linking Hydrogel.

[This corrects the article DOI: 10.3389/fmed.2021.643402.].