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Gastrointestinal (GI) cancer is one of the most common malignancies, and a leading cause of cancer-related death worldwide. However, molecular targeted therapies are still lacking, leading to poor treatment efficacies. As an important layer of epigenetic regulation, RNA N6-Methyladenosine (m6A) modification is recently linked to various biological hallmarks of cancer by orchestrating RNA metabolism, including RNA splicing, export, translation, and decay, which is partially involved in a novel biological process termed phase separation. Through these regulatory mechanisms, m6A dictates gene expression in a dynamic and reversible manner and may play oncogenic, tumor suppressive or context-dependent roles in GI tumorigenesis. Therefore, regulators and effectors of m6A, as well as their modified substrates, represent a novel class of molecular targets for cancer treatments. In this review, we comprehensively summarize recent advances in this field and highlight research findings that documented key roles of RNA m6A modification in governing hallmarks of GI cancers. From a historical perspective, milestone findings in m6A machinery are integrated with a timeline of developing m6A targeting compounds. These available chemical compounds, as well as other approaches that target core components of the RNA m6A pathway hold promises for clinical translational to treat human GI cancers. Further investigation on several outstanding issues, e.g. how oncogenic insults may disrupt m6A homeostasis, and how m6A modification impacts on the tumor microenvironment, may dissect novel mechanisms underlying human tumorigenesis and identifies next-generation anti-cancer therapeutics.

Three alternate TiN/AlN nanostructured multilayers with the TiN layer thicknesses of 60, 70, and 120 Å and the AlN layer thickness of 10 Å were fabricated using dc reactive magnetron sputtering. Microstructural characterizations of the three nano-scale films were performed using nonpolarized specular neutron reflectometry. The results showed that the three TiN/AlN multilayer thin films were typical superlattice films and the thicknesses of the TiN layer and AlN layer in the multilayers were consistent with the design thickness nearly. The interface roughness was asymmetric in all the samples. The interface of AlN growing on TiN was much sharper than that of TiN growing on AlN and the latter was the diffusion interface in the TiN/AlN multilayer films.

Purpose To assess the prevalence of autoimmune disease (AiD) in patients with primary open-angle glaucoma (POAG) undergoing ophthalmic surgery. Design Retrospective, cross-sectional study. Participants Patients with POAG undergoing any ophthalmic surgery and control subjects undergoing cataract surgery at the Massachusetts Eye and Ear from March 2019 to April 2020. Methods All available medical records with patient demographics, ocular, and medical conditions were reviewed. Differences in AiD prevalence were assessed and adjusted for covariates using multiple logistic regression. Additionally, a subgroup analysis comparing the POAG patients with and without AiD was performed. Main Outcome Measures To assess the prevalence of AiD based on the American Autoimmune Related Diseases Association list. Results A total of 172 patients with POAG and 179 controls were included. The overall prevalence of AiD was 17.4% in the POAG group and 10.1% in the controls (P = 0.044); 6.4% of POAG patients and 3.4% of controls had more than 1 AiD (P = 0.18). The most prevalent AiDs in POAG group were rheumatoid arthritis (4.6%) and psoriasis (4.1%), which were also the most common in controls (2.8% each). In a fully adjusted multiple logistic regression analysis accounting for steroid use, having an AiD was associated with 2.62-fold increased odds of POAG relative to controls (95% confidence interval, 1.27–5.36, P = 0.009); other risk factors for POAG derived from the analysis included age (odds ratio [OR], 1.04, P = 0.006), diabetes mellitus (OR, 2.31, P = 0.008), and non-White ethnicity (OR, 4.75, P 0.13, for both). Conclusions A higher prevalence of AiD was found in POAG patients compared with control patients undergoing ophthalmic surgery. The presence of AiD was associated with increased risk for POAG after adjusting for covariates. Additional factors may have prevented a difference in RNFL thickness in POAG patients with and without AiD. Autoimmunity should be explored further in the pathogenesis of POAG.

PURPOSE: Clinical models to identify patients at high risk of primary graft dysfunction (PGD) after heart transplantation (HT) are limited, and the underlying pathophysiology of this common post-transplant complication remains poorly understood. We sought to identify whether pre-transplant levels of circulating proteins reporting on immune activation and inflammation are associated with incident PGD. METHODS: The study population consisted of 219 adult heart transplant recipients identified between 2016 and 2020 at Duke University Medical Center, randomly divided into derivation (n = 131) and validation (n = 88) sets. PGD was defined using modified ISHLT criteria. Proteomic profiling was performed using Olink panels (n = 354 proteins) with serum samples collected immediately prior to transplantation. Association between normalized relative protein expression and PGD was tested using univariate and multivariable (recipient age, creatinine, mechanical circulatory support, and sex; donor age; ischemic time) models. Significant proteins identified in the derivation set (p < 0.05 in univariate models), were then tested in the validation set. Pathway enrichment analysis was used to test candidate biological processes. The predictive performance of proteins was compared to that of the RADIAL score. RESULTS: Nine proteins were associated with PGD in univariate models in the derivation set. Of these, only CLEC4C remained associated with PGD in the validation set after Bonferroni correction (OR [95% CI] = 3.04 [1.74,5.82], p = 2.8×10(−4)). Patterns of association were consistent for CLEC4C in analyses stratified by biventricular/left ventricular and isolated right ventricular PGD. Pathway analysis identified interferon-alpha response and C-type lectin signaling as significantly enriched biologic processes. The RADIAL score was a poor predictor of PGD (AUC = 0.55). CLEC4C alone (AUC = 0.66, p = 0.048) and in combination with the clinical covariates from the multivariable model (AUC = 0.69, p = 0.018) improved discrimination for the primary outcome. CONCLUSIONS: Pre-transplantation circulating levels of CLEC4C, a protein marker of plasmacytoid dendritic cells (pDCs), may identify HT recipients at risk for PGD. Further studies are needed to better understand the potential role pDCs and the innate immune response in PGD.

Although the Maastricht VI/Florence consensus report recommended high-dose proton pump inhibitor-amoxicillin dual therapy as possible rescue therapy forTo compare the efficacy, safety, patient compliance, and cost between high-dose dual therapy (HDDT) and culture-based susceptibility-guided therapy (CB-SGT) as a rescue regimen forA single-center, open-label, randomized controlled clinical trial.In all, 146 patients with a history of eradication failure were enrolled and randomly assigned to receive HDDT or CB-SGT. HDDT consisted of esomeprazole 20 mg and amoxicillin 750 mg, both given four times per day (qid). CB-SGT consisted of esomeprazole 20 mg twice daily (bid), amoxicillin 1000 mg bid plus clarithromycin 500 mg bid, metronidazole 400 mg bid, or levofloxacin 500 mg daily (qd) for sensitive patients, in that order. For patients with triple resistance, a bismuth-containing regimen with a high dose of metronidazole was chosen, including esomeprazole 20 mg bid, bismuth 220 mg bid, amoxicillin 1000 mg bid, and metronidazole 400 mg qid. All regimens were given for 14 days.The eradicationHDDT can reach an eradication rate of 85% in treatment-experienced patients ofThis clinical trial was registered at the Chinese Clinical Trail Registry (trail registration number: ChiCTR1900025044).

Epigenetic factors are known to influence tissue development, functionality, and their response to pathophysiology. This review will focus on different types of epigenetic regulators and their associated molecular apparatus that affect the optic nerve. A comprehensive understanding of epigenetic regulation in optic nerve development and homeostasis will help us unravel novel molecular pathways and pave the way to design blueprints for effective therapeutics to address optic nerve protection, repair, and regeneration.

Muller cells (MC) are considered dormant retinal progenitor cells in mammals. Previous studies demonstrated ephrin-As act as negative regulators of neural progenitor cells in the retina and brain. It remains unclear whether the lack of ephrin-A2/A3 is sufficient to promote the neurogenic potential of MC. Here we investigated whether the MC is the primary retinal cell type expressing ephrin-A2/A3 and their role on the neurogenic potential of Muller cells. In this study, we showed that ephrin-A2/A3 and their receptor EphA4 were expressed in retina and especially enriched in MC. The level of ephrinAs/EphA4 expression increased as the retina matured that is correlated with the reduced proliferative and progenitor cell potential of MC. Next, we investigated the proliferation in primary MC cultures isolated from wild-type and A2-/- A3-/- mice by 5-ethynyl-2'-deoxyuridine (EdU) incorporation. We detected a significant increase of EdU+ cells in MC derived from A2-/- A3-/- mice. Next, we investigated the role of ephrin-A2/A3 in mice undergoing photoreceptor degeneration such as Rhodopsin knockout (Rho-/-) mice. To further evaluate the role of ephrin-A2/A3 in MC proliferation in vivo, EdU was injected intraperitoneally to adult wild-type, A2-/- A3-/- , Rho-/- and Rho-/- A2-/- A3-/- mice and the numbers of EdU+ cells distributed among different layers of the retina. EphrinAs/EphA4 expression was upregulated in the retina of Rho-/- mice compared to the wild-type mice. In addition, cultured MC derived from ephrin-A2-/- A3-/- mice also expressed higher levels of progenitor cell markers and exhibited higher proliferation potential than those from wild-type mice. Interestingly, we detected a significant increase of EdU+ cells in the retinas of adult ephrin-A2-/- A3-/- mice mainly in the inner nuclear layer; and these EdU+ cells were co-localized with MC marker, cellular retinaldehyde-binding protein, suggesting some proliferating cells are from MC. In Rhodopsin knockout mice (Rho-/- A2-/- A3-/- mice), a significantly greater amount of EdU+ cells were located in the ciliary body, retina and RPE than that of Rho-/- mice. Comparing between 6 and 12 weeks old Rho-/- A2-/- A3-/- mice, we recorded more EdU+ cells in the outer nuclear layer in the 12-week-old mice undergoing severe retinal degeneration. Taken together, Ephrin-A2/A3 are negative regulators of the proliferative and neurogenic potentials of MC. Absence of ephrin-A2/A3 promotes the migration of proliferating cells into the outer nuclear layer and may lead to retinal cell regeneration. All experimental procedures were approved by the Animal Care and Use Committee at Schepens Eye Research Institute, USA (approval No. S-353-0715) on October 24, 2012.

There is a huge amount of microbial community in the human intestinal tract, among which the gut microbiota accounts for the largest proportion, which is crucial for maintaining the normal physiological function of human body. Gut microbiota imbalance not only affects gastrointestinal function, but also damages organ functions outside the gastrointestinal tract. Recently, scholars have put forward the doctrines of the "gut-liver" axis and the "gut-brain" axis based on the interrelation and influence between the intestine and other organs. With the deepening of research, the role of gut microbiota in the development and progression of lung diseases has been increasingly concerned, and the theory of "gut-lung" axis has been gradually formed, which is also consistent with the theory described in traditional medicine as "The lung stands in interior-exterior relationship with the large intestine". This paper mainly introduces the research progress of the "gut-lung" axis and lung-related diseases for providing a reference for the treatment of clinical lung diseases. DOI: 10.11855/j.issn.0577-7402.2020.11.12

Background Sensitized candidates with unacceptable antigens are a group that demands special attention in organ transplantation. Calculated panel reactive antigen (cPRA) is not used to modify allocation priorities in lung transplantation. The impact of cPRA on waiting list time and mortality is unknown. Methods We performed a retrospective review of candidates for lung transplantation listed from May 2005 to 2018. Data from the Organ Procurement and Transplantation Network/United Network for Organ Sharing STAR (Standard Analysis and Research) dataset was paired with additional unacceptable human leukocyte antigen (UA-HLA) data, which were used to calculate the listing cPRA. Candidates were stratified based on the lack of UA-HLAs or cPRA level for candidates with unacceptable antigens reported. Unadjusted competing risks and adjusted subdistribution hazard models were fit. Results A total of 29,085 candidates met inclusion criteria for analysis. Of these, 23,562 (81%) with no UA-HLAs, 3472 (11.9%) with a cPRA less than 50, and 2051 with a cPRA greater than or equal to 50 (7.1%). On adjusted analysis, a cPRA greater than or equal to 50 was independently associated with increased waitlist mortality at 1 year (hazard ratio, 1.71; 95% confidence interval, 1.55-1.88; P Conclusions Further evaluation of organ allocation with consideration of a candidate's cPRA may be warranted in order to optimize equity in access to transplants.

Retinal ischemic events, which result from occlusion of the ocular vasculature share similar causes as those for central nervous system stroke and are among the most common cause of acute and irreversible vision loss in elderly patients. Currently, there is no established treatment, and the condition often leaves patients with seriously impaired vision or blindness. The immune system, particularly T-cell- mediated responses, is thought to be intricately involved, but the exact roles remain elusive. We found that acute ischemia-reperfusion injury to the retina induced a prolonged phase of retinal ganglion cell loss that continued to progress during 8 weeks after the procedure. This phase was accompanied by microglial activation and CD4+ T-cell infiltration into the retina. Adoptive transfer of CD4+ T cells isolated from diseased mice exacerbated retinal ganglion cell loss in mice with retinal reperfusion damage. On the other hand, T-cell deficiency or administration of T-cell or interferon-gamma-neutralizing antibody attenuated retinal ganglion cell degeneration and retinal function loss after injury. These findings demonstrate a crucial role for T-cell-mediated responses in the pathogenesis of neural ischemia. These findings point to novel therapeutic targets of limiting or preventing neuron and function loss for currently untreatable conditions of optic neuropathy and/or central nervous system ischemic stroke.

Purpose Transcorneal electrical stimulation (TcES) is increasingly applied as a therapy for preserving and improving vision in retinal neurodegenerative and ischemic disorders. However, a common complaint about TcES is its induction of eye pain and dryness in the clinic, while the mechanisms remain unknown. Method TcES or transpalpebral ES (TpES) was conducted in C57BL6j mice for 14 days. The contralateral eyes were used as non-stimulated controls. Levels of intracellular [Ca2+] ([Ca2+]i) were assessed by Fura-2AM. The conductance resistances of the eye under various ES conditions were measured in vivo by an oscilloscope. Results Although TcES did not affect tear production, it significantly induced damage to the ocular surface, as revealed by corneal fluorescein staining that was accompanied by significantly decreased mucin (MUC) 4 expression compared to the control. Similar effects of ES were detected in cultured primary corneal epithelium cells, showing decreased MUC4 and ZO-1 levels after the ES in vitro. In addition, TcES decreased secretion of MUC5AC from the conjunctiva in vivo, which was also corroborated in goblet cell cultures, where ES significantly attenuated carbachol-induced [Ca2+]i increase. In contrast to TcES, transpalpebral ES (TpES) did not induce corneal fluorescein staining while significantly increasing tear production. Importantly, the conductive resistance from orbital skin to the TpES was significantly smaller than that from the cornea to the retina in TcES. Conclusion TcES, but not TpES, induces corneal epithelial damage in mice by disrupting mucin homeostasis. TpES thus may represent a safer and more effective ES approach for treating retinal neurodegeneration clinically.

The apolipoprotein E4 (APOE4) allele is associated with an increased risk of Alzheimer disease and a decreased risk of glaucoma, but the underlying mechanisms remain poorly understood. Here, we found that in two mouse glaucoma models, microglia transitioned to a neurodegenerative phenotype characterized by upregulation of Apoe and Lgals3 (Galectin-3), which were also upregulated in human glaucomatous retinas. Mice with targeted deletion of Apoe in microglia or carrying the human APOE4 allele were protected from retinal ganglion cell (RGC) loss, despite elevated intraocular pressure (IOP). Similarly to Apoe

Adenosine is an endogenous nucleoside that modulates many physiological processes. Adenosine is also a chemical mediator that regulates many physiological processes, including inflammation, ischemia and hypoxia. Its actions are mediated by interaction with specific cell membrane receptors. Four subtypes of adenosine receptors have been cloned: A1, A2A, A2B, and A3. Among there receptors, A2B receptor is one of the adenosine receptors with the lowest affinity with adenosine. In recent years, a large number of studies have shown that adenosine A2B receptor is involved in a variety of pathological and physiological processes of diseases. Herein, we try to review the recent advances made in the study of A2B receptor. DOI: 10.11855/j.issn.0577-7402.2019.12.13

In this work, the Co/Ni-free Na2/3Mn0.8Fe0.1Mg0.1O2 has been synthesized and investigated as low-cost and high–Mn content layered oxide cathode material for sodium-ion batteries by x-ray diffraction and electrochemical techniques. Due to a larger ionic size of Mg2+ than of Fe3+, the lattice parameters a and c both increase and the Mg2+ doping results in an expanded space for sodium-ion diffusion with the improved diffusion coefficient of sodium ion compared with Na2/3Mn0.8Fe0.2O2. Na2/3Mn0.8Fe0.1Mg0.1O2 delivers a high initial discharge capacity of 168 mAh g−1, and great rate capabilities of 102, 80, and 55 mAh g−1 at high rates of 2 C, 5 C, and 10 C. Mg2+ doping also can alleviate the Jahn-Teller effect by Mn3+ and stabilize the crystal structure, thus enhancing the cyclic stability of Na2/3Mn0.8Fe0.1Ti0.1O2 with about 90% capacity retention at 0.1 C. Electrochemical inactive and low-cost Mg-ion doping is an effective approach to improve the layered oxide cathode materials for sodium-ion batteries.

BACKGROUND: Donor-specific antibodies are associated with increased risk of antibody-mediated rejection and decreased allograft survival. Therefore, reducing the risk of these antibodies remains a clinical need in transplantation. Plasma cells are a logical target of therapy given their critical role in antibody production. METHODS: To target plasma cells, we treated sensitized rhesus macaques with daratumumab (anti-CD38 mAb). Before transplant, we sensitized eight macaques with two sequential skin grafts from MHC-mismatched donors; four of them were also desensitized with daratumumab and plerixafor (anti-CXCR4). We also treated two patients with daratumumab in the context of transplant. RESULTS: The animals treated with daratumumab had significantly reduced donor-specific antibody levels compared with untreated controls (57.9% versus 13% reduction; P

Dimer impurity in the solution of a generation five (G5) polyamidoamine (PAMAM) dendrimer has been investigated by small-angle neutron scattering (SANS). The existence of dimer impurity in dendrimer solution was evidenced by indirect Fourier transform (IFT) analysis of the SANS data, in which the maximum dimension of particles in solution was found to be about twice the diameter of G5 dendrimer. We then developed an analytical model which accounts for the scattering contribution from both dendrimer monomer and dimer. The experimental data were well fitted by using the established model. The results showed that the amount of dimer impurities is significant for the measured three batches of G5 PAMAM dendrimers.

Purpose Clinical manifestations of photoreceptor degeneration include gradual thinning of the outer nuclear layer (ONL) and progressive reduction of electroretinogram (ERG) amplitudes and vision loss. Although preclinical evaluations of treatment strategies greatly depend on rodent models, the courses of these changes in mice remain unclear. We thus sought to investigate the temporal correlations in changes of spatial vision, ERG response, and ONL thickness in mice with progressive photoreceptor degeneration. Methods Adult wild-type (WT) mice and mice carrying rhodopsin deficiency (Rho-/-), a frequently used mouse model of human retinitis pigmentosa, were selected for investigation. Mouse spatial vision, including visual acuity (VA) and contrast sensitivity (CS), was determined using optomotor response (OMR) assays; ONL thickness was quantified by spectral-domain optical coherence tomography (SD-OCT), and ERG was performed to evaluate retinal functions. The mice were killed when they were 14 weeks old, and the cone photoreceptors in retinal sections were counted. Results Spatial vision, ONL thickness, and ERG amplitudes remained stable in WT mice at all examined time points. While 6-week-old Rho-/- mice had VA, CS, as well as ERG responses similar to those of WT mice, progressive reductions in the spatial vision and retinal functions were recorded thereafter. Most tested 12-week-old Rho-/- mice had no visual-evoked OMR and ERG responses. Moreover, CS, but not VA, displayed a linear decline that was closely associated with ONL thinning, reduction of ERG amplitudes, and loss of cones. Conclusions We presented a comprehensive study of the relation between the changes of spatial vision, retinal function, and ONL thickness in postnatal week (PW)6 to PW12 Rho-/- mice. CS is a more sensitive indicator of spatial vision compared to VA, although both are required as separate parameters for monitoring the visual changes in retina undergoing photoreceptor degeneration.

Massive MIMO system has attracted attention due to it’s significant improvement in system capacity and spectrum utilization. Pilot pollution greatly limited the performance of Massive MIMO system. To optimize the pilot pollution in Massive MIMO system. In this paper, a pilot allocation scheme based on machine learning algorithm and users’ angle of arrival is proposed. The scheme firstly classified all users according to whether the users’ angle of arrival overlaps with each other. It randomly assigned pilot sequences to users whose angle of arrival do not overlap with each other. Secondly, it used machine learning algorithm to classify users whose angle of arrival overlap with each other into interfering group and non-interfering groups based on users’ location information. We assign orthogonal pilots to users in the interfering group and randomly assign pilot sequences to users in the non-interfering group. Simulation results show that when the number of antenna reached 300, the pilot efficiency can be increased by about 11.67%. The pilot allocation scheme proposed in this paper can effectively suppress the impact of pilot pollution on the performance of Massive MIMO system, improve pilot efficiency and reduce pilot overhead.

Ischemia is a common pathological condition present in many neurodegenerative diseases, including ischemic stroke, retinal vascular occlusion, diabetic retinopathy, and glaucoma, threatening the sight and lives of millions of people globally. Ischemia can trigger excessive oxidative stress, inflammation, and vascular dysfunction, leading to the disruption of tissue homeostasis and, ultimately, cell death. Current therapies are very limited and have a narrow time window for effective treatment. Thus, there is an urgent need to develop more effective therapeutic options for ischemia-induced neural injuries. With emerging reports on the pharmacological properties of natural flavonoids, these compounds present potent antioxidative, anti-inflammatory, and antiapoptotic agents for the treatment of ischemic insults. Three major active flavonoids, baicalein, baicalin, and wogonin, have been extracted from Scutellaria baicalensis Georgi (S. baicalensis); all of which are reported to have low cytotoxicity. They have been demonstrated to exert promising pharmacological capabilities in preventing cell and tissue damage. This review focuses on the therapeutic potentials of these flavonoids against ischemia-induced neurotoxicity and damage in the brain and retina. The bioactivity and bioavailability of baicalein, baicalin, and wogonin are also discussed. It is with hope that the therapeutic potential of these flavonoids can be utilized and developed as natural treatments for ischemia-induced injuries of the central nervous system (CNS).

The wide Mg alloy sheets produced by hot extrusion usually can easily form an inhomogeneous texture, resulting in anisotropic mechanical properties and poor formability. However, few studies have been carried out on the bulk texture investigation at different areas of as-extruded Mg alloy sheets, especially the Mg alloys with different alloying elements. In this work, the effect of Al on the bulk texture and mechanical properties at different areas for three wide Mg-Al-Zn alloy sheets with different Al contents (Mg-3Al-0.5Zn, Mg-8Al-0.5Zn and Mg-9Al-0.5Zn) are mainly investigated by neutron diffraction. The results showed that a strong and uneven basal texture was formed in the Mg-3Al-0.5Zn sheet. Meanwhile, the intensity of the basal texture was significantly weakened due to the numerous fine precipitates of Mg17Al12 particles, with the Al content increasing, which hinder the grain growth during extrusion, while fine recrystallized grains have a more random orientation. The enhanced tensile properties in Mg-8Al-0.5Zn and Mg-9Al-0.5Zn alloy sheets are ascribed to the cooperation effect of a refined microstructure, precipitates and weakened basal texture. Among the three Mg alloy sheets, the Mg-8Al-0.5Zn alloy sheet has a yield strength of about 270 MPa, an ultimate tensile strength of about 330 MPa and ultimate elongation of about 16% in the extrusion direction, which possesses the most excellent comprehensive mechanical properties.

Purpose To evaluate Nuclear Factor NF-κB (NF-κB) signaling on microglia activation, migration, and angiogenesis in laser-induced choroidal neovascularization (CNV). Methods Nine-week-old C57BL/6 male mice were randomly assigned to IMD-0354 treated or untreated groups (5 mice, 10 eyes per group). CNV was induced with a 532-nm laser. Laser spots (power 250 mW, spot size 100 μm, time of exposure 50 ms) were created in each eye using a slit-lamp delivery system. Selective inhibitor of nuclear factor kappa-B kinase subunit beta (IKK2) inhibitor IMD-0354 (10 μg) was delivered subconjunctivally; vehicle-treated mice were the control. The treatment effect on CNV development was assessed at five days post-CNV induction in vivo in C57BL/6 and Cx3cr1gfp/wt mice by fluorescent angiography, fundus imaging, and ex vivo by retinal flatmounts immunostaining and Western blot analysis of RPE/Choroidal/Scleral complexes (RCSC) lysates. In vitro evaluations of IMD-0354 effects were performed in the BV-2 microglial cell line using lipopolysaccharide (LPS) stimulation. Results IMD-0354 caused a significant reduction in the fluorescein leakage and size of the laser spot, as well as a reduction in microglial cell migration and suppression of phospho-IκBα, Vascular endothelial growth factor (VEGF-A), and Prostaglandin-endoperoxide synthase 2 (COX-2). In vivo and ex vivo observations demonstrated reduced lesion size in mice, CD68, and Allograft inflammatory factor 1 (IBA-1) positive microglia cells migration to the laser injury site in IMD-0354 treated eyes. The data further corroborate with GFP-positive cells infiltration of the CNV site in Cx3cr1wt/gfp mice. In vitro IMD-0354 (10–25 ng/ml) treatment reduced NF-κB activation, expression of COX-2, caused decreased Actin-F presence and organization, resulting in reduced BV-2 cells migration capacity. Conclusion The present data indicate that NF-κB activation in microglia and it's migration capacity is involved in the development of laser CNV in mice. Its suppression by NF-κB inhibition might be a promising therapeutic strategy for wet AMD.