Th17 cells in glaucoma patients promote Ig production in IL-17A and IL-21-dependent manner.

Elevated expression of autoantibodies is a hallmark of immune dysregulation in glaucoma and may cause retinal ganglion cell apoptosis and immune-mediated nerve damage, thus contributing to the development of blindness. The cause of autoantibody upregulation remains unclear. Th17 cells are shown to promote autoimmunity and Ig production. Here, we demonstrate that the serum levels of interleukin (IL)-17A and IL-21 are comparable between glaucoma patients and non-glaucoma controls. However, the levels of Th17-promoting cytokines, such as tumour necrosis factor (TNF) IL-6, are higher in glaucoma patients than in controls. Subsequently, we demonstrate that glaucoma patients present upregulated levels of Th17 cells that are quiescent directly ex vivo. Interestingly, compared to the Th17 cells from non-glaucoma subjects, the Th17 cells from glaucoma patients present similar IL-17A production capacity but significantly higher IL-21 production capacity. Given that IL-21 is also described as a specific cytokine of follicular helper T cells, the Ig production by B cells following co-incubation with circulating Th17 cells is investigated. Th17 cells from glaucoma patients present significantly enhanced potential to promote Ig production than the Th17 cells from controls. Both glaucoma patient Th17 cells and control Th17 cells require IL-17A and IL-21 for Ig production. Overall, results from this study suggest that Th17 cells from glaucoma patients present elevated capacity to stimulate Ig production.

Long Non-coding RNA SPAG5-AS1 Attenuates Diabetic Retinal Vascular Dysfunction by Inhibiting Human Retinal Microvascular Endothelial Cell Proliferation, Migration, and Tube Formation by Regulating the MicroRNA-1224-5p/IRS-1 Axis.

Diabetic retinopathy (DR) is causal for visual impairment and blindness. The research aimed at whether and how lncRNA SPAG5-AS1 (SPAG5-AS1) is involved in retinal vascular dysfunction under diabetic conditions. After determination of SPAG5-AS1, miR-1224-5p, and IRS-1 expression in high glucose (HG)-treated human retinal microvascular endothelial cells (hRMECs), their respective influences on retinal vascular dysfunction was explored by cell counting kit-8, Transwell, wound-healing assay, and tube formation assay. SPAG5-AS1/miR-1224-5p/IRS-1 interaction was identified through bioinformatics analysis and luciferase reporter gene assays. As tested, SPAG5-AS1 and IRS-1 levels were induced, while miR-1224-5p was enhanced in HG-treated hRMECs. Up-regulating SPAG5-AS1 or downregulating miR-1224-5p could inhibit hRMECs proliferation, migration, and tube formation, and vice versa. SPAG5-AS1 can promote IRS-1 expression by miR-1224-5p, and depletion of IRS-1 was functional for the reversal of up-regulated SPAG5-AS1-modified influences on HG-treated hRMECs. Additionally, in diabetic rats, SPAG5-AS1 can alleviate retinal vascular dysfunction. All in all, SPAG5-AS1 attenuates diabetic retinal vascular dysfunction through miR-1224-5p/IRS-1 axis, providing a potential therapeutic strategy for DR.

Down-regulation of LCN2 attenuates retinal vascular dysfunction and caspase-1-mediated pyroptosis in diabetes mellitus.

Background: Diabetic retinopathy (DR) is a diabetic microangiopathy with increasing incidence, which seriously threatens the quality of life of patients. This study investigated the molecular regulation mechanism of lipocalin-2 (LCN2) in DR by targeting the function of human retinal vascular endothelial cells (HRVECs). Methods: The expression of LCN2 in the retinal tissue of diabetic and high glucose (HG)-induced HRVECs was detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR) analysis and western blotting assay. After intravitreal injection of adeno-associated virus (AAV)-NC or AAV-sh-LCN2, in vivo experiments, hematoxylin and eosin (H&E) staining, and retinal trypsin digestion experiments were performed to analyze the effect of LCN2 silencing on DR retinal tissue. Terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) staining was used to evaluate apoptosis and immunohistochemical (IHC) staining was performed to detect the expressions of caspase-1. Western blot was used to detect the expressions of pyroptosis-associated proteins. After transfection of sh-NC and sh-LCN2, the function of HRVECs cells induced by HG was evaluated by wound healing assay, Transwell assay, and tube formation assay. Results: The expression of LCN2 was significantly up-regulated in diabetic retinal tissue and HG-induced HRVECs. In vivo experiments showed that LCN2 silencing can significantly reduce diabetic retinal injury. Cell function experiments also revealed that LCN2 silencing inhibited cell migration, invasion, and angiogenesis. Flow cytometry and immunofluorescence staining showed that downregulation of LCN2 could inhibit caspase-1 mediated pyroptosis in HG-induced HRVECs. Conclusions: Down-regulation of LCN2 can significantly inhibit cell migration, invasion, and angiopoiesis, and pyroptosis regulated by caspase-1, thus attenuating the progression of DR.

Meta-Analysis of Long-Term Efficacy of Proliferative Diabetic Retinopathy Based on Intelligent Medical Treatment.

In order to solve some problems of subhealth and high chronic diseases, the diagnosis and treatment of value-added diabetic retinopathy are studied. In particular, diabetes, a high chronic disease, poses a great threat to people's health. With the continuous improvement of national health awareness, the medical field also begins to pay more attention to the diagnosis and treatment of value-added diabetic retinopathy. In order to improve the long-term treatment of value-added diabetic retinopathy through intelligent medical monitoring and systematic scientific efficacy analysis and evaluation, the purpose of this study is to explore how to effectively achieve the meta-analysis of long-term efficacy of proliferative diabetic retinopathy through intelligent medical treatment. Through the study of diabetic retinopathy, the system can help doctors to achieve unlimited further signs of parameter acquisition and transmission and build more mature after treatment of the results of the monitoring platform. At the same time, a conclusion based on vitrectomy was proposed to effectively improve the surgical efficacy of patients with proliferative diabetic retinopathy.

Interlinked Microcone Resistive Sensors Based on Self-Assembly Carbon Nanotubes Film for Monitoring of Signals.

Flexible pressure sensors still face difficulties achieving a constantly adaptable micronanostructure of substrate materials. Interlinked microcone resistive sensors were fabricated by polydimethylsiloxane (PDMS) nanocone array. PDMS nanocone array was achieved by the second transferring tapered polymethyl methacrylate (PMMA) structure. In addition, self-assembly 2D carbon nanotubes (CNTs) networks as a conducting layer were prepared by a low-cost, dependable, and ultrafast Langmuir−Blodgett (LB) process. In addition, the self-assembled two-dimensional carbon nanotubes (CNTs) network as a conductive layer can change the internal resistance due to pressure. The results showed that the interlinked sensor with a nanocone structure can detect the external pressure by the change of resistivity and had a sensitive resistance change in the low pressure (<200 Pa), good stability through 2800 cycles, and a detection limit of 10 kPa. Based on these properties, the electric signals were tested, including swallowing throat, finger bending, finger pressing, and paper folding. The simulation model of the sensors with different structural parameters under external pressure was established. With the advantages of high sensitivity, stability, and wide detection range, this sensor shows great potential for monitoring human motion and can be used in wearable devices.

Microdome-Tunable Graphene/Carbon Nanotubes Pressure Sensors Based on Polystyrene Array for Wearable Electronics.

Resistive pressure sensors are appealing due to having several advantages, such as simple reading mechanisms, simple construction, and quick dynamic response. Achieving a constantly changeable microstructure of sensing materials is critical for the flexible pressure sensor and remains a difficulty. Herein, a flexible, tunable resistive pressure sensors is developed via simple, low-cost microsphere self-assembly and graphene/carbon nanotubes (CNTs) solution drop coating. The sensor uses polystyrene (PS) microspheres to construct an interlocked dome microstructure with graphene/CNTs as a conductive filler. The results indicate that the interlocked microdome-type pressure sensor has better sensitivity than the single microdome-type and single planar-type without surface microstructure. The pressure sensor's sensitivity can be adjusted by varying the diameter of PS microspheres. In addition, the resistance of the sensor is also tunable by adjusting the number of graphene/CNT conductive coating layers. The developed flexible pressure sensor effectively detected human finger bending, demonstrating tremendous potential in human motion monitoring.

Can neuroprotection effectively manage primary open-angle glaucoma? a protocol of systematic review and meta-analysis.

BACKGROUND: This study aims to assess the efficacy of neuroprotection (NP) for the management of patients with primary open-angle glaucoma (POAG). METHODS: A comprehensive search will be carried out from the beginning to the February 29, 2020 in the electronic databases: Scopus, Web of Science, PUBMED, EMBASE, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, WANGFANG, and China National Knowledge Infrastructure. There are no limitations related to the language and publication date. Two researchers will independently undertake study selection from searched literatures, extract data from included trials, and appraise study quality using Cochrane risk of bias tool. Any disagreements will be solved by a third researcher through consultation. RevMan 5.3 software will be employed for statistical analysis. RESULTS: This study will provide a high-quality synthesis of randomized controlled trials of NP for the management of patients with POAG. CONCLUSIONS: The results of this study will help to create proposals for the treatment of POAG using NP. SYSTEMATIC REVIEW REGISTRATION: INPLASY202040107.

Can dorzolamide/timolol-fixed combination effectively treat primary open-angle glaucoma?: A protocol for systematic review and meta-analysis.

BACKGROUND: Primary open-angle glaucoma (POAG) is a very common disorder, and it is the second leading cause that results in blindness worldwide after cataracts. Previous studies have reported that dorzolamide/timolol-fixed combination (DTFC) can be used in treating POAG. However, there are still inconsistent results. Thus, this study will systematically investigate the efficacy and safety of DTFC on POAG. METHODS: A comprehensive search will be carried out in Cochrane Library, MEDLINE, EMBASE, CINAHI, ACMD, China National Knowledge Infrastructure, and WANGFANG database from origin to the present. There are no limitations related to the language and publication status. Only randomized controlled trials that assessed the efficacy and safety of DTFC for the treatment of POAG will be included. Two researchers will independently undertake record selection, data extraction, and study quality assessment. Any divisions will be solved by discussion with a third researcher. We will perform statistical analysis using RevMan 5.3 software RESULTS:: This study will summarize the present evidence to identify the efficacy and safety of DTFC in treating POAG through mean intraocular pressure, best corrected visual acuity, contrast sensitivity, bioelectric activity of the retina, rate of progression of glaucoma, quality of life, and adverse events. CONCLUSIONS: The results of this study will provide evidence of DTFC for the treatment of POAG. SYSTEMATIC REVIEW REGISTRATION: INPLASY202040120.

Therapeutic effect of lutein supplement on non-proliferative diabetic retinopathy: A retrospective study.

This study retrospectively evaluated the effect of lutein supplement (LS) on patients with non-proliferative diabetic retinopathy (NPDR).A total of 72 patients with NPDR were included in this study. All patients received Zeaxanthin during the study period. In addition, 36 patients also received LS and were assigned to the treatment group, while the other 36 patients did not receive LS and were assigned to the control group. All patients were treated for a total of 4 months. The endpoints included visual acuity (VA), contrast sensitivity (CS), and glare sensitivity (GS). In addition, any adverse events were also assessed. All endpoints were measured before and after 4-month treatment.Before treatment, there were no significant differences in VA (P = .75), CS (P = .71), and GS (P = .73) between two groups. After 4-month treatment, there were still no significant differences in all endpoints of VA (P = .66), CS (P = .58), and GS (P = .61) between two groups. No adverse events were recorded in either group.The results of this retrospective study showed that LS may not benefit for patients with NPDR after 4-month treatment. More high quality randomized controlled trials should still be needed to warrant the results of this study.

Efficacy of fenofibrate for diabetic retinopathy: A systematic review protocol.

BACKGROUND: Numerous studies have reported the efficacy of fenofibrate for patients with diabetic retinopathy (DRP). No systematic review has, however, addressed its efficacy for DRP. Thus, this systematic review will firstly evaluate the efficacy and safety of fenofibrate for patients with DRP. METHODS: This study will search the following databases: PUMBED, EMBASE, CINAHI, ACMD, CENTRAL, CBM, CNKI, VIP, and WANGFANG, along with grey literature from inception to the present. We will accept randomized controlled trials on evaluating the efficacy and safety of fenofibrate for DRP. The primary outcome is the progression of DRP. The secondary outcomes are vision loss, development of diabetic macular edema, aggravation of hard exudates, quality of life, and any adverse events. Methodological quality of each included study will be assessed by using Cochrane Collaboration risk of bias tool. In addition, Grading of Recommendations Assessment, Development and Evaluation tool will also be used to evaluate the overall strength of the evidence. Two independent reviewers will conduct all procedures of study selection, data extraction, and methodological assessment. Any disagreements will be consulted with a third reviewer. RevMan 5.3 software will be used to pool data and to carry out the meta-analysis if it is possible. RESULTS: In present study, we anticipate to find a considerable number of published studies presenting evidence on efficacy and safety of fenofibrate for DRP. CONCLUSION: The findings of this systematic review will provide latest evidence of fenofibrate for patients with DRP. DISSEMINATION AND ETHICS: The findings of this scoping review will be disseminated in print, conferences, or by peer-reviewed journals. No ethical approval is needed for this systematic review, because it is a literature-based study. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019121869.

Efficacy of ranibizumab for the treatment of diabetic retinopathy: A protocol for systematic review of randomized controlled trial.

BACKGROUND: Previous clinical trials have reported that ranibizumab can be used to treat diabetic retinopathy (DR) effectively. However, no study has been conducted to evaluate its efficacy for patients with DR systematically. Thus, this study will specifically and systematically assess the efficacy and safety of ranibizumab for DR. METHODS: Cochrane Library, EMBASE, PUBMED, Web of Science, Google Scholar, Cumulative Index to Nursing and Allied Health Literature, China National Knowledge Infrastructure, and Chinese Biomedical Literature Database will be searched from inceptions to the March 20, 2019 for studies related to the topic. This study will only consider publicly released randomized controlled trials for evaluating the effect and safety of ranibizumab for DR. No language restrictions will be imposed for all databases search. Methodological quality of each included trial will be assessed by Cochrane risk of bias tool. Statistical analysis will be performed by Stata 12.0 software. RESULTS: This study will provide recent summary evidence of ranibizumab for DR. Primary outcomes include percentages with retinopathy improvement, and cumulative probabilities for retinopathy worsening. Secondary outcome consist of visual function, best-corrected visual acuities, central subfield thickness, total macular volume, peripheral visual field loss, retinal neovascularization, and adverse events. CONCLUSION: The findings of this study may provide theoretical basis for clinical practice refer and may benefit more patients with DR.