IC100, a humanized therapeutic monoclonal anti-ASC antibody alleviates oxygen-induced retinopathy in mice DOI Creative Commons

Huijun Yuan,

Shaoyi Chen,

Matthew R. Duncan

et al.

Angiogenesis, Journal Year: 2024, Volume and Issue: 27(3), P. 423 - 440

Published: May 6, 2024

Abstract Background Retinopathy of prematurity (ROP), which often presents with bronchopulmonary dysplasia (BPD), is among the most common morbidities affecting extremely premature infants and a leading cause severe vision impairment in children worldwide. Activations inflammasome cascade microglia have been implicated playing role development both ROP BPD. Apoptosis-associated speck-like protein containing caspase recruitment domain (ASC) pivotal assembly. Utilizing mouse models oxygen-induced retinopathy (OIR) BPD, this study was designed to test hypothesis that hyperoxia induces ASC speck formation, leads microglial activation retinopathy, inhibition formation by humanized monoclonal antibody, IC100, directed against ASC, will ameliorate abnormal retinal vascular formation. Methods We first tested retina ASC-citrine reporter mice expressing fusion C-terminal citrine (fluorescent GFP isoform) using BPD model causes lung eye injury exposing newborn room air (RA) or 85% O 2 from postnatal day (P) 1 P14. The retinas were dissected on P14 flat mounts used detect endothelium AF-594-conjugated isolectin B4 (IB4) citrine-tagged specks. To assess effects IC100 an OIR model, wildtype (C57BL/6 J) exposed RA P1 P6, then 75% P7 P11, P12 P18. At randomized following groups: placebo PBS (RA-PBS), (O -PBS), + intravitreal injection -IC100-IVT), intraperitoneal -IC100-IP). Retinal vascularization evaluated mount staining IB4. Microglial detected immunofluorescence for allograft inflammatory factor (AIF-1) CD206. structure analyzed H&E-stained sections, function pattern electroretinography (PERG). RNA-sequencing (RNA-seq) performed determine transcriptional treatment OIR. Results specks significantly increased exposure colocalized vasculature models, associated activation. Treatment IC100-IVT IC100-IP reduced vaso-obliteration neovascularization. also activation, restored structure, improved function. RNA-seq showed corrected induction genes angiogenesis, leukocyte migration, VEGF signaling caused . suppression cell junction assembly, neuron projection, recognition Conclusion These data demonstrate crucial pathogenesis efficacy therapeutic anti-ASC antibody treating mice. Thus, may potentially be considered diseases oxygen stresses such as ROP.

Language: Английский

From Inflammasomes to Pyroptosis: Molecular Mechanisms in Chronic Intestinal Diseases — Opportunity or Challenge? DOI Creative Commons
Jintao Fang,

Weihan Zhu,

Dian Yu

et al.

Journal of Inflammation Research, Journal Year: 2025, Volume and Issue: Volume 18, P. 3349 - 3360

Published: March 1, 2025

Pyroptosis is a unique form of programmed cell death characterized by intense inflammation. It involves the activation Gasdermin proteins, which membrane pores, leading to rapid rupture and release inflammatory molecules. Unlike other types death, pyroptosis has distinct mechanisms plays complex role in chronic intestinal diseases, including bowel disease, fibrosis, infectious enteritis, colorectal cancer. This review comprehensively examines how influences disease development progression while exploring therapeutic potential targeting pyroptosis-related pathways. Moreover, interplay between gut microbiota summarized, highlighting its critical pathogenesis disorders. A deeper understanding these diseases may provide valuable insights for future research contribute innovative strategies gastroenterology.

Language: Английский

Citations

0
New Insights on the Potential Role of Pyroptosis in Parkinson’s Neuropathology and Therapeutic Targeting of NLRP3 Inflammasome with Recent Advances in Nanoparticle-Based miRNA Therapeutics DOI
‏Hebatallah M. Saad, Esraa A. Salem,

A. Elsayed

et al.

Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown

Published: March 18, 2025

Language: Английский

Citations

0
Sodium fluoride promotes myopia progression via the activation of the ferroptosis pathway by PIEZO1 and pharmacological targeting PIEZO1 represents an innovative approach for myopia treatment DOI Creative Commons
Bo Liu,

Xueting Yao,

Qinying Huang

et al.

Cell Biology and Toxicology, Journal Year: 2025, Volume and Issue: 41(1)

Published: April 2, 2025

Sodium fluoride-induced ocular damage constitutes a significant public health concern globally; however, the precise molecular mechanisms underlying this issue remain obscure. This study aims to investigate effects of sodium fluoride on myopia and offer novel theoretical foundations for future strategies in prevention control. The experimental data showed that could promote progression, through bioinformatics analysis, we found affect ferroptosis pathway. Western blotting redox kit assays further confirmed activates We also demonstrated PIEZO1 plays crucial role myopia, inhibitor (GsMTx4) can inhibit Subsequently, identified as potential target baicalin, which inhibited expression vivo vitro, by docking modeling CETSA assays. Finally, baicalin via PIEZO1. Taken together, our findings indicate progression activating pathway PIEZO1, targeting delay may provide new drug treatment future.

Language: Английский

Citations

0
Changes in the Expression Profile of Pyroptosis-Related Genes in Senescent Retinal Pigment Epithelial Cells after Lutein Treatment DOI Creative Commons
Barbara Strzałka‐Mrozik, Marcel Madej, Natalia Kurowska

et al.

Current Issues in Molecular Biology, Journal Year: 2023, Volume and Issue: 45(2), P. 1500 - 1518

Published: Feb. 9, 2023

Retinal pigment epithelium (RPE) is a specialized structure essential for proper vision, which constantly exposed to oxidative damage. With aging, this damage accumulates within the RPE cells, causing various diseases, including age-related macular degeneration (AMD). Numerous antioxidant substances are used prevent process in humans, lutein. This study aims determine differences expression patterns of pyroptosis genes senescent human retinal epithelial cell line ARPE-19 Changes pyroptosis-related were assessed by oligonucleotide microarrays, and results validated real-time RT-qPCR. The microarray analysis showed seven transcripts differentially expressed both H2O2-treated cells versus controls lutein/H2O2-treated compared (FC > 2.0). Depending on lutein, H2O2, or co-treatment statistically significant TXNIP, CXCL8, BAX, CASP1 confirmed RT-qPCR (p < 0.05). A STRING database that proteins encoded analyzed form strong interaction network 0.001). These data indicate lutein modulates level genes, may be useful development new methods preventing pathway activation future.

Language: Английский

Citations

10
IC100, a humanized therapeutic monoclonal anti-ASC antibody alleviates oxygen-induced retinopathy in mice DOI Creative Commons

Huijun Yuan,

Shaoyi Chen,

Matthew R. Duncan

et al.

Angiogenesis, Journal Year: 2024, Volume and Issue: 27(3), P. 423 - 440

Published: May 6, 2024

Abstract Background Retinopathy of prematurity (ROP), which often presents with bronchopulmonary dysplasia (BPD), is among the most common morbidities affecting extremely premature infants and a leading cause severe vision impairment in children worldwide. Activations inflammasome cascade microglia have been implicated playing role development both ROP BPD. Apoptosis-associated speck-like protein containing caspase recruitment domain (ASC) pivotal assembly. Utilizing mouse models oxygen-induced retinopathy (OIR) BPD, this study was designed to test hypothesis that hyperoxia induces ASC speck formation, leads microglial activation retinopathy, inhibition formation by humanized monoclonal antibody, IC100, directed against ASC, will ameliorate abnormal retinal vascular formation. Methods We first tested retina ASC-citrine reporter mice expressing fusion C-terminal citrine (fluorescent GFP isoform) using BPD model causes lung eye injury exposing newborn room air (RA) or 85% O 2 from postnatal day (P) 1 P14. The retinas were dissected on P14 flat mounts used detect endothelium AF-594-conjugated isolectin B4 (IB4) citrine-tagged specks. To assess effects IC100 an OIR model, wildtype (C57BL/6 J) exposed RA P1 P6, then 75% P7 P11, P12 P18. At randomized following groups: placebo PBS (RA-PBS), (O -PBS), + intravitreal injection -IC100-IVT), intraperitoneal -IC100-IP). Retinal vascularization evaluated mount staining IB4. Microglial detected immunofluorescence for allograft inflammatory factor (AIF-1) CD206. structure analyzed H&E-stained sections, function pattern electroretinography (PERG). RNA-sequencing (RNA-seq) performed determine transcriptional treatment OIR. Results specks significantly increased exposure colocalized vasculature models, associated activation. Treatment IC100-IVT IC100-IP reduced vaso-obliteration neovascularization. also activation, restored structure, improved function. RNA-seq showed corrected induction genes angiogenesis, leukocyte migration, VEGF signaling caused . suppression cell junction assembly, neuron projection, recognition Conclusion These data demonstrate crucial pathogenesis efficacy therapeutic anti-ASC antibody treating mice. Thus, may potentially be considered diseases oxygen stresses such as ROP.

Language: Английский

Citations

3