Comparative analysis of inflammatory response in the BALB/c and C57BL/6 mouse strains in an endotoxin-induced uveitis model

Magaña‐Guerrero, Fátima Sofía; Quiroz-Mercado, Joaquín; Garfias-Zenteno, Nicolás; Garfias, Yonathan

doi:10.1016/j.jim.2019.112677

Cited by 7 publications

(6 citation statements)

References 25 publications

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“…A massive influx of cells was observed in the vitreous body and iris, accompanied by iris vascular dilatation at 24 hpi, and then spontaneously resolved at 72 hpi. The characteristic of rapid inflammation resolution in zebrafish was basically consistent with EIU model in mouse ( 8 , 27 ). It would be of great significance to further explore the mechanism underlying the rapid resolution and short disease course, with the hope to provide new strategies for disease control and treatment in human.…”

Section: Discussionsupporting

confidence: 74%

A novel uveitis model induced by lipopolysaccharide in zebrafish

Xiao

Liu²,

Su³

et al. 2022

Front. Immunol.

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ObjectiveEndotoxin-induced uveitis (EIU) is an important tool for human uveitis study. This study was designed to develop a novel EIU model in zebrafish.MethodsAn EIU model in zebrafish was induced by intravitreal lipopolysaccharide (LPS) injection and was assessed dynamically. Optical coherence tomography (OCT) was used to assess infiltrating cells in the vitreous body. The histological changes wereevaluated using HE staining and immune cells were measured by immunofluorescence. The retinal RNA Sequencing (RNA-Seq) was used to explore the transcriptional changes during inflammation. RNA-Seq data were analyzed using time-course sequencing data analysis (TCseq), ClueGO plugin in Cytoscape, and Gene Set Enrichment Analysis (GSEA) software. Flow cytometry and retinal flat mounts were used to dynamically quantify the immune cells.ResultsEIU was successfully induced in zebrafish following intravitreal LPS injection. Inflammation appeared at 4 hours post injection (hpi), reached its peak at 24 hpi, and then resolved at 72 hpi. Immunofluorescence confirmed that massive influx ofneutrophils into the iris and vitreous body, and activation of microglia as evidenced by ameboid-shaped appearance in the retina. Retinal RNA-seq during the EIU course identified four gene clusters with distinct expression characteristics related to Toll-likereceptor signaling pathway, cytokine-cytokine receptor interaction, NOD-like receptor signaling pathway, and extracellular matrix (ECM)-receptor interaction, respectively. Prednisone immersion inhibited the inflammatory response of EIU in zebrafish, whichwas confirmed by decreased neutrophils detected in flow cytometry and retinal flat mounts.ConclusionsWe developed a novel EIU model in zebrafish, which may be particularly useful for gene-editing and high-throughput screening of new drugs for the prevention and treatment of uveitis.

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Section: Discussionsupporting

confidence: 74%

A novel uveitis model induced by lipopolysaccharide in zebrafish

Xiao

Liu²,

Su³

et al. 2022

Front. Immunol.

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“…EIU was induced as previously described 24 . Briefly, 6‐ to 8‐week‐old mice were anesthetized with intraperitoneal injection of phenobarbitone (50 mg/kg body weight), and pupils were dilated with 0.5% tropicamide.…”

Section: Methodsmentioning

confidence: 99%

“…EIU was induced as previously described. 24 Briefly, 6-to 8-week-old mice were anesthetized with intraperitoneal injection of phenobarbitone (50 mg/kg body weight), and pupils were dilated with 0.5% tropicamide. EIU was induced by a single intravitreal injection of 125 ng LPS dissolved in 1 μL of PBS (L2630, E. coli 0111: B4, Sigma-Aldrich, St Louis, MO, USA).…”

Section: Eiu and Saa Treatmentmentioning

confidence: 99%

Serum amyloid A aggravates endotoxin‐induced ocular inflammation through the regulation of retinal microglial activation

Feng,

Zhou,

Yang

et al. 2023

The FASEB Journal

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Serum amyloid A (SAA) are major acute‐phase response proteins which actively participate in many inflammatory diseases. This study was designed to explore the function of SAA in acute ocular inflammation and the underlying mechanism. We found that SAA3 was upregulated in endotoxin‐induced uveitis (EIU) mouse model, and it was primarily expressed in microglia. Recombinant SAA protein augmented intraocular inflammation in EIU, while the inhibition of Saa3 by siRNA effectively alleviated the inflammatory responses and rescued the retina from EIU‐induced structural and functional damage. Further study showed that the recombinant SAA protein activated microglia, causing characteristic morphological changes and driving them further to pro‐inflammatory status. The downregulation of Saa3 halted the amoeboid change of microglia, reduced the secretion of pro‐inflammatory factors, and increased the expression of tissue‐reparative genes. SAA3 also regulated the autophagic activity of microglial cells. Finally, we showed that the above effect of SAA on microglial cells was at least partially mediated through the expression and signaling of Toll‐like receptor 4 (TLR4). Collectively, our study suggested that microglial cell‐expressed SAA could be a potential target in treating acute ocular inflammation.

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“…Inflammation, a key factor in many diseases, may be accompanied by oxidative stress; together, these processes act as cooperative and even synergistic partners in worsening the pathogenesis of several diseases. Lipopolysaccharides (LPSs), i.e., heat-stable cell wall components of Gram-negative bacteria, which are known as endotoxins and pathogenassociated molecular patterns (PAMPs), are often employed in the search to induce a variety of pathophysiological effects, inflammatory diseases, and autoimmune disorders [1][2][3][4].…”

Section: Introductionmentioning

confidence: 99%

Protective Effects of Fucoxanthin Dampen Pathogen-Associated Molecular Pattern (PAMP) Lipopolysaccharide-Induced Inflammatory Action and Elevated Intraocular Pressure by Activating Nrf2 Signaling and Generating Reactive Oxygen Species

et al. 2021

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Inflammation and oxidative stress are closely related processes in the pathogenesis of various ocular diseases. Uveitis is a disorder of the uvea and ocular tissues that causes extreme pain, decreases visual acuity, and can eventually lead to blindness. The pharmacological functions of fucoxanthin, isolated from brown algae, induce a variety of therapeutic effects such as oxidative stress reduction and repression of inflammation reactions. However, the specific anti-inflammatory effects of fucoxanthin on pathogen-associated molecular pattern (PAMP) lipopolysaccharide-induced uveitis have yet to be extensively described. Therefore, the aim of present study was to investigate the anti-inflammatory effects of fucoxanthin on uveitis in rats. The results showed that fucoxanthin effectively enhanced the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) in ocular tissues. Furthermore, fucoxanthin significantly increased the ocular activities of superoxide dismutase and decreased the levels of malondialdehyde stimulated by PAMP-induced uveitis. Ocular hypertension and the levels of inflammatory cells and proinflammatory cytokine tumor necrosis factor-alpha in the aqueous humor were alleviated with fucoxanthin treatment. Consequently, compared to the observed effects in lipopolysaccharide groups, fucoxanthin treatment significantly preserved iris sphincter innervation and pupillary function. Additionally, PAMP-induced corneal endothelial disruption was significantly inhibited by fucoxanthin treatment. Overall, these findings suggest that fucoxanthin may protect against inflammation from PAMP-induced uveitis by promoting the Nrf2 pathway and inhibiting oxidative stress.

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Comparative analysis of inflammatory response in the BALB/c and C57BL/6 mouse strains in an endotoxin-induced uveitis model

Cited by 7 publications

References 25 publications

A novel uveitis model induced by lipopolysaccharide in zebrafish

A novel uveitis model induced by lipopolysaccharide in zebrafish

Serum amyloid A aggravates endotoxin‐induced ocular inflammation through the regulation of retinal microglial activation

Protective Effects of Fucoxanthin Dampen Pathogen-Associated Molecular Pattern (PAMP) Lipopolysaccharide-Induced Inflammatory Action and Elevated Intraocular Pressure by Activating Nrf2 Signaling and Generating Reactive Oxygen Species

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