Anti-TNFα and Anti-IL-1β Monoclonal Antibodies Preserve BV-2 Microglial Homeostasis Under Hypoxia by Mitigating Inflammatory Reactivity and ATF4/MAPK-Mediated Apoptosis DOI Creative Commons
Linglin Zhang,

Chaoqiang Guan,

S. Wang

et al.

Antioxidants, Journal Year: 2025, Volume and Issue: 14(3), P. 363 - 363

Published: March 19, 2025

The disruption of microglial homeostasis and cytokine release are critical for neuroinflammation post-injury strongly implicated in retinal neurodegenerative diseases like glaucoma. This study examines responses to chemical hypoxia induced by cobalt chloride (CoCl2) BV-2 murine cells, focusing on signaling pathways proteomic alterations. We assessed the protective effects monoclonal antibodies against TNFα IL-1β. CoCl2 exposure led decreased cell viability, reduced mitochondrial membrane potential, increased lactate dehydrogenase release, elevated reactive oxygen species generation, activation inflammatory pathways, including nitric oxide synthase (iNOS), STAT1, NF-κB/NLRP3. These were significantly mitigated treatment with anti-TNFα anti-IL-1β, suggesting their dual role reducing damage inhibiting reactivity. Additionally, these treatments apoptosis modulating ATF4 p38 MAPK/caspase-3 pathways. Label-free quantitative mass spectrometry-based proteomics Gene Ontology revealed that upregulation proteins primarily involved endoplasmic reticulum catabolic processes, while downregulated associated biosynthesis. Anti-TNFα anti-IL-1β partially restored profile toward normalcy, network analysis identifying heat shock protein family A member 8 (HSPA8) as a central mediator recovery. findings offer insights into pathogenesis hypoxic impairment suggest potential therapeutic targets.

Language: Английский

Aldose reductase inhibition decelerates optic nerve degeneration by alleviating retinal microglia activation DOI Creative Commons
Mishal Rao,

Yukai Huang,

Chia-Chun Liu

et al.

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: April 5, 2023

As part of the central nervous system (CNS), retinal ganglion cells (RGCs) and their axons are only neurons in retina that transmit visual signals from eye to brain via optic nerve (ON). Unfortunately, they do not regenerate upon injury mammals. In ON trauma, microglia (RMG) become activated, inducing inflammatory responses resulting axon degeneration RGC loss. Since aldose reductase (AR) is an response mediator highly expressed RMG, we investigated if pharmacological inhibition AR can attenuate ocular inflammation thereby promote survival regeneration after crush (ONC). vitro, discovered Sorbinil, inhibitor, attenuates BV2 activation migration lipopolysaccharide (LPS) monocyte chemoattractant protein-1 (MCP-1) treatments. vivo, Sorbinil suppressed ONC-induced Iba1 + microglia/macrophage infiltration promoted survival. Moreover, restored function delayed one week ONC. RNA sequencing data revealed protects by suppressing signaling. summary, report first study demonstrating transiently degeneration, providing a potential therapeutic strategy for neuropathies.

Language: Английский

Citations

14
The role of astrocyte in neuroinflammation in traumatic brain injury DOI Creative Commons
Liang He, Ruqiang Zhang,

Maiqiao Yang

et al.

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2023, Volume and Issue: 1870(3), P. 166992 - 166992

Published: Dec. 19, 2023

Language: Английский

Citations

13
Rapamycin suppresses neuroinflammation and protects retinal ganglion cell loss after optic nerve crush DOI

Feifei Wang,

Yuning Song, Peiyu Liu

et al.

International Immunopharmacology, Journal Year: 2023, Volume and Issue: 119, P. 110171 - 110171

Published: April 14, 2023

Language: Английский

Citations

12
Whole-eye transplantation: Current challenges and future perspectives DOI Open Access
Anna Scarabosio, Pier Luigi Surico, Vlad Tereshenko

et al.

World Journal of Transplantation, Journal Year: 2024, Volume and Issue: 14(2)

Published: June 13, 2024

Whole-eye transplantation emerges as a frontier in ophthalmology, promising transformative approach to irreversible blindness. Despite advancements, formidable challenges persist. Preservation of donor eye viability post-enucleation necessitates meticulous surgical techniques optimize retinal integrity and ganglion cell survival. Overcoming the inhibitory milieu central nervous system for successful optic nerve regeneration remains elusive, prompting exploration neurotrophic support immunomodulatory interventions. Immunological tolerance, paramount graft acceptance, confronts distinctive immunogenicity ocular tissues, driving research into targeted immunosuppression strategies. Ethical legal considerations underscore necessity stringent standards ethical frameworks. Interdisciplinary collaboration ongoing endeavors are imperative navigate these complexities. Biomaterials, stem therapies, precision immunomodulation represent avenues this pursuit. Ultimately, aim review is critically assess current landscape whole-eye transplantation, elucidating advancements while delineating future directions clinical practice. Through concerted efforts, stands revolutionize ophthalmic care, offering hope restored vision enhanced quality life those afflicted with

Language: Английский

Citations

4
Early prevention of carrageenan-induced peripheral/spinal inflammation suppresses microglial hyperreactivity in the trigeminal spinal subnucleus caudalis and alleviates chronic facial nociception DOI Creative Commons
Toru Yamamoto, Mitsuhiro Yoshida,

Yuhei Koyama

et al.

Heliyon, Journal Year: 2025, Volume and Issue: 11(2), P. e41602 - e41602

Published: Jan. 1, 2025

In this study, we investigated the mechanisms underlying carrageenan-induced chronic pain and therapeutic effect of anti-inflammatory drug meloxicam. Rats were injected with 3 % carrageenan into masseter muscle. These rats exhibited acute hypersensitivity to mechanical stimuli for 6 weeks after injection. Pre-treatment meloxicam prevented hypersensitivity. Furthermore, minocycline dexamethasone, but not acetaminophen, suppressed in phase. Microglial reactivity trigeminal spinal subnucleus caudalis (Vc) was assessed by immunohistochemistry days treatment. The microglial cells Vc increased carrageenan-treated compared vehicle-injected rats. Meloxicam hyperreactivity Vc. results suggest that early prevention peripheral/spinal inflammation suppresses inhibits development orofacial pain.

Language: Английский

Citations

0
A review of pharmacological mechanisms, challenges and prospects of macromolecular glycopeptides DOI
Ye Gao, Xiaoyi Chen, Jin‐Ao Duan

et al.

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: unknown, P. 140294 - 140294

Published: Jan. 1, 2025

Language: Английский

Citations

0
The gut microbiota regulates diabetic retinopathy in adult rats DOI Creative Commons

Jueyu Hou,

Zhongping Lv,

Yujiao Wang

et al.

Frontiers in Microbiology, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 29, 2025

Introduction Diabetic retinopathy (DR) is the most common complication of diabetes. Neuronal apoptosis, activated microglia, and microvascular changes are early features DR. The gut microbiota critical for maturation activation microglia in brain, DR patients exhibit dysbiosis. However, effect on retinal under normal or diabetic conditions still unclear. Methods Type 2 diabetes (T2D) was established male adult Brown Norway (BN) rats, they were treated with gavage broad-spectrum antibiotic (ABX) suspension. Retinal fundus fluorescein angiography performed to observe dynamic growth process leakage blood vessels. Retro-orbital injection FITC-Dextran blood-retinal barriers. After treatment ABX lasting more than 6 months, 16S RNA sequencing stool samples determine microbiome mass spectrometry used analyze metabolome changes. IBA1, IB4, Brn3 staining rats’ wholemount sections vessels number ganglion cells. Results Long-term (6 months) T2D caused dysbiosis increased average taxa numbers. We showed that antibiotics (ABXs) can reduce BN rats without T2D. Interestingly, months a loss cells (RGCs) significant vascular reduced alleviated RGC damage these rats. Conclusion Our data suggests gavage-induced alleviate long-term Targeting may be future therapeutic strategy management.

Language: Английский

Citations

0
Double-edge sword: Positive and negative effects of inflammation on axonal regeneration DOI

Alexander W. Venanzi,

Abigail S. Hackam

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown, P. 85 - 101

Published: Jan. 1, 2025

Language: Английский

Citations

0
Immune-responsive gene 1/itaconate pathway inhibits microglia activation to alleviate traumatic optic neuropathy in mice DOI
J.-F. Deng, Feng Zhou,

A Luodan

et al.

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 149, P. 114199 - 114199

Published: Feb. 3, 2025

Language: Английский

Citations

0
The impact of circadian rhythms on retinal immunity DOI
He Ren,

Yilin Yuan,

Dong Zhang

et al.

Chronobiology International, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 15

Published: Feb. 7, 2025

The eye is an immune-protected organ, which driven by factors such as cytokines, chemicals, light, and mechanical stimuli. circadian clock intrinsic timing mechanism that influences the immune activities, cell count activity, well inflammatory responses. Recent studies have demonstrated also possesses rhythm, this rhythmic regulation participates in ocular modulation. In review, we discuss immunoregulatory mechanisms of within eye, reveal new perspectives for prevention treatment diseases.

Language: Английский

Citations

0