Inflammation plays a pivotal role in ischemia-induced retinal neovascularization. Targeting microglia/macrophage-based neuroinflammation presents a promising therapeutic strategy. Ferulic acid (FA), a natural and active ingredient in plants, exerts favorable anti-oxidative and anti-inflammatory activities. In this study, we investigated the inhibitory effect of FA against hypoxia-induced retinal angiogenesis using cultured retinal vascular endothelial cells and an oxygen-induced retinopathy mouse (OIR) model. The immunoregulatory effect of FA on microglia/macrophage polarization was evaluated by detecting the expression of specific markers for both pro-inflammatory “M1” and anti-inflammatory “M2” phenotypes using co-immunostaining and polymerase chain reaction assays. The underlying molecular mechanism upon FA treatment was also explored. The results showed that FA supplement markedly inhibited retinal pathological angiogenesis both in vivo and in vitro . In addition, FA switched microglia/macrophage polarization from “M1” towards “M2” phenotype and alleviated the inflammatory response. Mechanically, the anti-angiogenic and anti-inflammatory properties of FA were mainly due to blockade of the ROS/NF-κB pathway. Our data demonstrated an anti-angiogenic effect of FA through regulating M1-to-M2 microglia/macrophage polarization, suggesting a potential therapeutic strategy for retinal neovascular diseases.
To evaluate the efficacy and safety of adequate silicone oil (SO) tamponade procedure in patients with complicated retinal detachment.Thirty-one eyes in 31 patients were enrolled in this prospective case series. Adequate SO tamponade was performed by injecting the SO into the vitreous cavity and the entire anterior chamber, followed by posterior capsulotomy and inferior peripheral iridotomy. Preoperative and follow-up data including retinal anatomic reattachment and SO status, best-corrected visual acuity, intraocular pressure, surgical complications and management were collected and analyzed.Twenty-nine eyes presented with complete retinal reattachment after subsequent SO removal with a primary success rate of 93.5%. Seventeen patients (54.8%) had complete anterior chamber SO migration to the vitreous cavity within the first postoperative day. The average time for anterior chamber SO migration was 2.3 ± 1.8 days. No oil-fluid interface in the vitreous cavity was observed in all the eyes, indicating a relatively adequate SO tamponade. Acute intraocular pressure elevation occurred in 16 (51.6%) eyes and was controllable under medication (n = 16) and anterior chamber paracentesis (n = 1). Two patients developed recurrent retinal detachment and received SO removal and a secondary adequate SO tamponade. At final follow-up, all the eyes had SO removal for at least 3 months and retinas maintained completely attached.The adequate SO tamponade procedure offers a simple, safe, and efficacious treatment alternative for complicated retinal detachment.
Significance Retinopathy is the leading cause of blindness, and development of effective therapy is urgently needed. Here, we defined an unprecedented subgroup of microglia that is responsible for causing retinopathy under hypoxia. Mechanistic studies demonstrated the signaling pathway of hypoxia-induced necroptosis of retinal microglia, i.e., the hypoxia–RIP1–RIP3–MLKL signaling axis, triggered an explosive release of FGF2, which in its turn to induce retinal neovascularization. Simultaneous targeting of necroptosis–FGF2 pathway and VEGF produces synergistic effects for treating retinopathy. On the basis of our findings, we propose a concept of necroptotic microglia-induced retinal angiogenesis and highlight a combination therapy for effective treatment of retinopathy.
Purpose: To integrate a massive open online course (MOOC) into conventional clinical ophthalmology teaching and investigate its impact on the skills of medical students. Methods: This was a nonrandomized, prospective, and comparative study. Seventy-six medical students were assigned to 2 groups before their clinical teaching. Some were asked to follow a MOOC for slitlamp microscope examination but used textbook for preview of visual acuity test (SLMM group, n=39), while others were required to take a MOOC for visual acuity test and previewed slitlamp microscopy using textbook (VATM group, n=37). All the students then underwent conventional clinical ophthalmology teaching on slitlamp microscopy and visual acuity test. Their performance was evaluated using Direct Observation of Procedural Skills (DOPS). Students were also asked to complete a 5-item questionnaire about their learning experience and comment on the MOOC. Results: Students in the SLMM group obtained overall higher scores in the slitlamp practical skills (47.64±4.01 vs 44.68±5.99, P=0.013), while those in the VATM group performed better in the visual acuity test (46.45±4.90 vs 43.78±4.94, P=0.004). MOOC was deemed to increase learning interests (4.13 of 5 points) and motivation (4.01 of 5 points) but was more preferred as an additional tool to traditional teaching methods (4.34 of 5 points) rather than to replace them (2.92 of 5 points). Conclusions: MOOC offers an added benefit in improving clinical skills and is worth advocating as an additional tool for clinical ophthalmic education.
Background/Aims: Platelet-derived growth factors (PDGFs) have emerged as pivotal in pathological angiogenesis, which is a hallmark of various tumors and retinal diseases. Here we evaluated the anti-angiogenic effect of imatinib, an inhibitor of PDGF receptors α and β (PDGFR-α and -β), in retinal neovascularization using an oxygen-induced retinopathy (OIR) model. Methods: The OIR model was established and given imatinib or vehicle treatments daily from P12 to P16. At the peak of angiogenesis at P17, the neovascularization area was quantified on retinal whole-mounts with isolectin B4 staining. Immunofluorescence staining and western blots were used to determine the effect of imatinib on different vascular cells and the pathway molecules involved. Results: Imatinib effectively suppressed pathological angiogenesis in OIR mice and reduced the number of all three types of vascular cells, including endothelial cells, pericytes, and smooth muscle cells. Moreover, the expression and activation of PDGFR-α and -β were inhibited by imatinib. The imatinib-treated OIR mice presented with reduced expression of other potent pro-angiogenic factors such as VEGF and FGF2. No obvious retinal or systemic side effects were observed in the imatinib treatment group. Conclusions: Imatinib appears to be safe and effective in suppressing retinal neovascularization. Targeting PDGFs/PDGFRs may also be important for anti-angiogenic treatment and offer a viable alternative treatment for retinal angiogenic diseases.
Diabetic retinopathy (DR) is a leading cause of blindness that poses significant public health concerns worldwide. Increasing evidence suggests that neuroinflammation plays a key role in the early stages of DR. Microglia, long-lived immune cells in the central nervous system, can become activated in response to pathological insults and contribute to retinal neuroinflammation. However, the molecular mechanisms of microglial activation during the early stages of DR are not fully understood. In this study, we used in vivo and in vitro assays to investigate the role of microglial activation in the early pathogenesis of DR. We found that activated microglia triggered an inflammatory cascade through a process called necroptosis, a newly discovered pathway of regulated cell death. In the diabetic retina, key components of the necroptotic machinery, including RIP1, RIP3, and MLKL, were highly expressed and mainly localized in activated microglia. Knockdown of RIP3 in DR mice reduced microglial necroptosis and decreased pro-inflammatory cytokines. Additionally, blocking necroptosis with the specific inhibitor GSK-872 improved retinal neuroinflammation and neurodegeneration, as well as visual function in diabetic mice. RIP3-mediated necroptosis was activated and contributed to inflammation in BV2 microglia under hyperglycaemic conditions. Our data demonstrate the importance of microglial necroptosis in retinal neuroinflammation related to diabetes and suggest that targeting necroptosis in microglia may be a promising therapeutic strategy for the early stages of DR.
Flexible quantum dotlight‐emitting diodes (QLEDs) are demonstrated by using hot‐pressing AgNWs as the transparent conductive electrode and EGaIn as the back electrode. Both AgNWs and EGaIn are printable, and thus the whole device can be fabricated via vacuum‐free processes. The hot‐pressing AgNWs electrode exhibits excellent physical characteristics such as high transparency of 96.7% in the visible spectral region, and low sheet resistance of 28 Ω/sq. With the AgNWs and EGaIn, vacuum‐free‐fabricated QLEDs are successfully achieved with efficiency 13.2cd/A. Because of the elimination of the costly vacuum processes, the proposed fabrication processes are low cost and allow rapid fabrication of flexible QLEDs with high performance.
Abstract At present, many cloning selection algorithms have been studied, and improvements have been made to the cloning, mutation and selection steps. However, there is a lack of research on the optimization of the updating operation steps. The clonal selection algorithm is traditionally updated through a random complement of antibodies, which is a blind and uncertain process. The added antibodies may gather near a local optimal solution, resulting in the need for more iterations to obtain the global optimal solution. To solve this problem, our improved algorithm introduces a crowding degree factor in the antibody updating stage to determine whether there is crowding between antibodies. By eliminating antibodies with high crowding potential and poor affinity, the improved algorithm guides the antibodies to update in the direction of the global optimal solution and ensures stable convergence with fewer iterations. Experimental results show that the overall performance of the improved algorithm is 1% higher than that of the clonal selection algorithm and 2.2% higher than that of the genetic algorithm, indicating that the improved algorithm is effective. The improved algorithm is also transplanted to other improved clonal selection algorithms, and the overall performance is improved by 0.97%, indicating that the improved algorithm can be a beneficial supplement to other improved clonal selection algorithms.
We investigated the transmission of 100-Gb/s PAM4 signals using 850-nm VCSELs over 150-m MMFs with lateral offsets. The oxide aperture size of VCSEL, coupling loss and modal dispersion induced by misalignments are evaluated by simulations.
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