Astragalus polysaccharide attenuates retinal ischemia reperfusion-induced microglial activation through sortilin-related vacuolar protein sorting 10 domain containing receptor 2/laminin subunit alpha 1 upregulation

CytoJournal, Journal Year: 2025, Volume and Issue: 22, P. 2 - 2

Published: Jan. 7, 2025

Microglial activation is a hallmark of pathogenic retinal conditions such as ischemia-reperfusion (RIR). While sortilin-related vacuolar protein sorting 10 domain containing receptor 2 (Sorcs2) and laminin subunit alpha 1 (Lama1) have been implicated in neuroinflammatory processes, their roles regulating microglial RIR are not reported. The current work studied the potential Sorcs2 Lama1 negative regulators assessed therapeutic Astragalus polysaccharide (AP). Transcriptome profiling was conducted specimens group 72 h after induction. Oxygen-glucose deprivation/reperfusion (OGD/R) rat cells employed cellular induction model RIR. functional role dictating investigated vitro vivo using lentivirus-based gene expression. Further, effect AP on RIR-mediated investigated. were identified two downregulated genes samples following OGD/R triggered pro-inflammatory induced downregulation Lama1. or overexpression hindered OGD/R-induced attenuated inflammatory expansion microglia RIR-induced samples. treatment able to neutralize oxidative stress, promote expression Lama1, suppress activation. Our findings pinpoint could be an antioxidant attenuate ameliorate damages

Language: Английский

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Preclinical Retinal Disease Models: Applications in Drug Development and Translational Research

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(3), P. 293 - 293

Published: Feb. 21, 2025

Retinal models play a pivotal role in translational drug development, bridging preclinical research and therapeutic applications for both ocular systemic diseases. This review highlights the retina as an ideal organ studying advanced therapies, thanks to its immune privilege, vascular neuronal networks, accessibility, imaging capabilities. Preclinical retinal disease offer unparalleled insights into inflammation, angiogenesis, fibrosis, hypoxia, utilizing clinically translatable bioimaging tools like fundoscopy, optical coherence tomography, confocal scanning laser ophthalmoscopy, fluorescein angiography, optokinetic tracking, electroretinography. These have driven innovations anti-inflammatory, anti-angiogenic, neuroprotective strategies, with broader implications diseases such rheumatoid arthritis, Alzheimer’s, fibrosis-related conditions. By emphasizing integration of 3Rs principles novel modalities, this how not only enhances precision but also minimizes ethical concerns, paving way more predictive human-relevant approaches development.

Language: Английский

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Discovery of Endothelial–Monocyte Crosstalk in Ischemic‐Reperfusion Injury Following Liver Transplantation Based on Integration of Single‐Cell RNA and Transcriptome RNA Sequencing

Journal of Cellular and Molecular Medicine, Journal Year: 2025, Volume and Issue: 29(4)

Published: Feb. 1, 2025

ABSTRACT Hepatic ischemia/reperfusion injury (IRI) commonly complicates liver transplantation (LT). However, the precise mechanisms underlying hepatic IRI remain incompletely understood. We acquired single‐cell RNA sequencing (scRNA‐seq) and transcriptome data of LT patients from GEO database. Employing scRNA‐seq, we delved into interplay between non‐immune immune cells in IRI, pinpointing genes exhibiting altered expression patterns. Integrating insights gleaned scRNA‐seq datasets, deepened our comprehension cellular interactions IRI. Additionally, conducted preliminary validation identified gene alterations using immunofluorescence techniques. Using detected significant changes populations sinusoidal endothelial (LSECs) monocytes after ischemia–reperfusion (IRI). By integrating with bulk data, key dysregulated LSECs (ICAM1, SOCS3, NFKBIZ, JUND, TNFRSF12A HSPA6) (SOCS3, FPR2 NR4A2). Our analysis cell communication indicated that ANXA1‐FPR2 axis might be a pivotal signature mediating monocytes. then established mouse model for further analyses flow cytometry showed increase monocyte proportion post‐IR ( p < 0.01). Consistently, Western Blot also revealed upregulation ANXA1 study elucidated signalling pathways following The likely triggers cascade events, promoting infiltration amplifying inflammatory responses, thus worsening deleterious effects

Language: Английский

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Preserving blood-retinal barrier integrity: a path to retinal ganglion cell protection in glaucoma and traumatic optic neuropathy

Cell Regeneration, Journal Year: 2025, Volume and Issue: 14(1)

Published: April 2, 2025

Retinal ganglion cells (RGCs) are the visual gateway of brain, with their axons converging to form optic nerve, making them most vulnerable target in diseases such as glaucoma and traumatic neuropathy (TON). In both diseases, disruption blood-retinal barrier(BRB) is considered an important mechanism that accelerates RGC degeneration hinders axon regeneration. The BRB consists inner barrier (iBRB) outer (oBRB), which maintained by endothelial cells(ECs), pericytes(PCs), retinal pigment epithelial (RPE), respectively. Their functions include regulating nutrient exchange, oxidative stress, immune microenvironment. However, TON, structural functional integrity severely damaged due mechanical inflammatory reactions, metabolic disorders. Emerging evidence highlights leads heightened vascular permeability, cell infiltration, sustained chronic inflammation, creating a hostile microenvironment for survival. Furthermore, dynamic interplay imbalance among ECs, PCs, glial within neurovascular unit (NVU) pivotal drivers destruction, exacerbating apoptosis limiting nerve intricate molecular cellular mechanisms underlying these processes underscore BRB's critical role TON pathophysiology while offering compelling foundation therapeutic strategies targeting repair stabilization. This review provides crucial insights lays robust groundwork advancing research on neural regeneration innovative protective strategies.

Language: Английский

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Ganglion cell-derived LysoPS induces retinal neovascularisation by activating the microglial GPR34-PI3K-AKT-NINJ1 axis

Journal of Neuroinflammation, Journal Year: 2024, Volume and Issue: 21(1)

Published: Oct. 28, 2024

Retinal neovascularisation is a major cause of blindness in patients with proliferative diabetic retinopathy (PDR). It mediated by the complex interaction between dysfunctional ganglion cells, microglia, and vascular endothelial cells. Notably, retinal intrinsic immune cells retina, play crucial role pathogenesis retinopathy. In this study, we found that lysophosphatidylserines (LysoPS) released from injured induced microglial extracellular trap formation neovascularisation. Mechanistically, LysoPS activated GPR34-PI3K-AKT-NINJ1 signalling axis interacting GPR34 receptor on microglia. This activation upregulated expression inflammatory cytokines, such as IL-6, IL-8, VEGFA, FGF2, facilitated cell angiogenesis. As result, inhibition significantly decreased suppressing LysoPS-induced responses, both vitro vivo. study reveals apoptotic activating inflammation PDR, thereby enhancing our understanding

Language: Английский

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