Journal of Inflammation-London最新文献

{"title":"Exploring the mitigating potential of anthocyanin Malvidin in a mouse model of bleomycin-induced pulmonary fibrosis by inhibiting NLRP3 inflammasome activation and oxidative stress.","authors":"Dingzi Zhou, Lin Cai, Jie Xu, Daigang Fu, Ling Yan, Linshen Xie","doi":"10.1186/s12950-025-00441-1","DOIUrl":"10.1186/s12950-025-00441-1","url":null,"abstract":"<p><strong>Background: </strong>Malvidin (MV), an essential anthocyanin, has antioxidant and anti-inflammatory effects that may help treat pulmonary fibrosis (PF), a progressive and occasionally fatal condition characterized by severe lung scarring, oxidative stress, and inflammation.</p><p><strong>Objective: </strong>This study aims to evaluate the therapeutic potential of MV in PF by assessing its effects on inflammation, oxidative stress, and fibrotic markers through in vitro and in vivo models.</p><p><strong>Methods and materials: </strong>The compound was evaluated by molecular docking. BEAS-2B and RLE-6TN cells were treated with 200 µg/mL BLM to induce inflammation, followed by MV treatment. Cell viability, ROS levels, and wound healing were analyzed. In vivo, BLM-induced mice were evaluated to assess fibrotic and antioxidant biomarkers.</p><p><strong>Results: </strong>MV interacted with NLRP3 with a binding energy of -7 kcal/mol. MV increased cell viability in BLM-induced cells, reducing ROS and oxidative stress. Wound healing was enhanced in MV-treated groups. A decrease in HYP proteins confirms MV's antifibrotic effects. In the mice model, MV reduced TXNIP, MDA, and MPO while increasing CAT, GSH, and SOD, confirming its antioxidant capacity.</p><p><strong>Conclusion: </strong>MV alleviated PF in the BLM-induced model via the NLRP3 inflammasome pathway, demonstrating its potential as an antifibrotic and antioxidant agent.</p>","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"22 1","pages":"14"},"PeriodicalIF":4.4,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11959746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143756181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Semaphorin 7a is protective through immune modulation during acetaminophen-induced liver injury.","authors":"Eilidh J Livingstone, Jennifer A Cartwright, Lara Campana, Philip J Starkey Lewis, Benjamin J Dwyer, Rhona Aird, Tak Yung Man, Matthieu Vermeren, Adriano Giorgio Rossi, Luke Boulter, Stuart John Forbes","doi":"10.1186/s12950-025-00429-x","DOIUrl":"10.1186/s12950-025-00429-x","url":null,"abstract":"<p><strong>Background and aim: </strong>Acetaminophen (APAP) induced acute liver injury (ALI), the leading cause acute liver failure in the western world, has limited treatment options. APAP toxicity results in massive hepatic necrosis and secondary infiltrating monocytes and neutrophils, which contribute to pathogenesis. Semaphorin 7a (Sema7a), a chemoattractant and modulator of monocytes and neutrophils, is a potential therapeutic target in other conditions, but its role in APAP-ALI is unexplored.</p><p><strong>Methods: </strong>Wild-type (WT) and Sema7a knockout (KO) mice were examined during APAP-ALI. Serum liver function tests, histological analysis and cellular localisation of Sema7a and its receptors, Plexin C1 and Integrin β1, were examined. Serum cytokines were quantified, tissue macrophages and neutrophils were localised, and in vivo phenotype, including phagocytosis, was assessed by immunohistochemistry and flow cytometry.</p><p><strong>Results: </strong>Sema7a was expressed by HNF4α + peri-necrotic hepatocytes circumferentially during APAP-ALI injury phases, and serum concentrations were increased, and correlated with hepatic injury. Sema7a KO mice had increased circulating inflammatory cytokines and significantly less hepatic F4/80 + macrophages, a cell type required for hepatic repair. Sema7a KO mice had higher necrotic area neutrophils, and increased neutrophil chemoattractant CXCL1. Without Sema7a expression, mice displayed increased necrosis and liver injury markers compared to Sema7a WT mice. Without peri-necrotic hepatocyte Sema7a expression, we also identified increased cell death and hepatic cellular stress outside of necrosis.</p><p><strong>Conclusion: </strong>We have identified a novel protective role of Sema7a during injury phases of APAP-ALI. Without peri-necrotic hepatocyte Sema7a expression and secretion, there is increased inflammation, time specific worsened hepatic necrosis and increased hepatic cell stress and death outside of the necrotic zone.</p>","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"22 1","pages":"13"},"PeriodicalIF":4.4,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11927371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prehospital pulse-dose glucocorticoid on index of microvascular resistance in patients with ST-segment elevation myocardial infarction: a sub-study of the PULSE-MI trial.","authors":"Jasmine Melissa Marquard, Jacob Lønborg, Laust Emil Roelsgaard Obling, Rasmus Paulin Beske, Yan Zhou, Lars Nepper-Christensen, Niels Vejlstrup, Lia Evi Bang, Christian Hassager, Fredrik Folke, Lars Bredevang Andersen, Helle Collatz Christensen, Lene Holmvang, Frants Pedersen, Ole Ahlehoff, Reza Jabbari, Mikko Minkkinen, Rikke Sørensen, Hans-Henrik Tilsted, Thomas Engstrøm","doi":"10.1186/s12950-025-00440-2","DOIUrl":"10.1186/s12950-025-00440-2","url":null,"abstract":"<p><strong>Background: </strong>Microvascular injury in patients with ST-segment elevation myocardial infarction (STEMI) occurs in up to 50%, yet no therapeutic target exists. Inflammation contributes directly to myocardial damage in STEMI and may also cause deleteriously effects on the microcirculation. The aim of this prespecified sub-study was to determine the effect of prehospital pulse-dose glucocorticoid on the microcirculation determined by index of microvascular resistance (IMR) and its relation to inflammation. The PULSE-MI trial was a 1:1 randomized, blinded, placebo-controlled clinical trial in patients with STEMI transferred for primary percutaneous coronary intervention (PCI) investigating the cardioprotective effects of prehospital pulse-dose glucocorticoid (methylprednisolone 250 mg) compared with placebo. In this prespecified sub-study, we investigated microvascular function as IMR by thermodilution after primary PCI and inflammation defined by C-reactive protein (CRP) at 24 hours after onset of STEMI.</p><p><strong>Results: </strong>Of 530 patients included in the PULSE-MI trial, 295 (56%) were assessed with coronary physiology of whom 142 (48%) were treated with glucocorticoid and 153 (52%) with placebo. Baseline characteristics were overall well-balanced in both groups. The median IMR in the glucocorticoid group was 23 (interquartile range (IQR), 11-38) and 18 (IQR, 11-42) in the placebo group (p=0.49). CRP upon arrival did not differ between treatment groups (p=0.81), but CRP at 24 hours was significantly lower in the glucocorticoid group compared to placebo (p<0.001).</p><p><strong>Conclusions: </strong>Prehospital glucocorticoid did not impact IMR assessed immediately after primary PCI, albeit this compound, demonstrated significant anti-inflammatory effects as determined by CRP levels at 24 hours.</p><p><strong>Trial registration: </strong>http://www.</p><p><strong>Clinicaltrials: </strong>gov ; Unique Identifier: NCT05462730.</p>","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"22 1","pages":"12"},"PeriodicalIF":4.4,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143659792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Contribution of brain pericytes to neuroinflammation following repetitive head trauma.","authors":"Arianna Cembran, Maxwell Eisenbaum, Daniel Paris, Michael Mullan, Fiona Crawford, Scott Ferguson, Corbin Bachmeier","doi":"10.1186/s12950-025-00439-9","DOIUrl":"10.1186/s12950-025-00439-9","url":null,"abstract":"<p><strong>Background: </strong>Neuroinflammation is a prominent pathological hallmark of traumatic brain injury (TBI) and glia cells have been widely characterized in the onset or progression of brain inflammation. While an effect of inflammation on cerebrovascular breakdown has been observed, little is known about the specific contribution of brain pericytes to the inflammatory response in TBI. Here, we focused on studying the pericyte response to inflammatory stimuli commonly found in the brain following TBI.</p><p><strong>Methods: </strong>Mouse brain vascular pericytes were exposed to IL-1β, TNF-α and IFN-γ for 2 h and 24 h and probed for markers of pericyte health and a panel of inflammatory mediators. As the platelet-derived growth factor (PDGF) pathway is critical to pericyte function, we also assessed the effect of PDGF-BB stimulation on the inflammatory response in pericytes. Cultured pericytes were treated with PDGF-BB (10 ng/mL) prior to, simultaneously, and following inflammatory insult. To further investigate their role in brain immunosurveillance, we analyzed the cytokine secretome in mouse pericyte cultures treated with PDGF-BB, as well as in brain vascular pericytes isolated from repetitive mild TBI (r-mTBI) mice that were fed phenytoin-enriched chow, an inducer of PDGF-BB secretion.</p><p><strong>Results: </strong>Cytokine stimulation with TNF-α, IL-1β, and IFN-γ for 2 and 24 h led to significant upregulation of PDGFRβ in cultured pericytes, with an 8-fold increase after 24 h. MTT assays showed no significant change in cell viability, indicating that cytokine treatment did not induce cytotoxicity. Further, elevated levels of pro-inflammatory markers STAT1 and p-NFkB were observed in response to cytokine exposure, with a concurrent increase in VCAM1 and MMP9 expression. PDGF-BB treatment significantly attenuated the inflammatory response in pericytes, reducing PDGFRβ levels and the activation of inflammatory pathways, including STAT1 and NFkB. Cytokine secretion profiles also revealed that PDGF-BB, when administered post-inflammatory insult, selectively reduced pro-inflammatory cytokines such as IL-1β and IFN-γ. Additionally, phenytoin treatment in r-mTBI mice decreased IL-1β, TNF-α, IL-5, and KC/GRO levels in isolated brain pericytes, while IL-2, IL-4, and IL-6 levels were unchanged compared to untreated r-mTBI animals.</p><p><strong>Conclusions: </strong>Our results indicate an immunoreactive role for brain pericytes in the propagation of neuroinflammation. Moreover, following brain insults, we found PDGF-BB stimulation can normalize pericyte function and reduce cerebrovascular inflammation, a key factor in secondary brain injury. Targeting brain pericytes may provide novel therapeutic opportunities to improve cerebrovascular health and reduce brain inflammation in the aftermath of TBI.</p>","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"22 1","pages":"11"},"PeriodicalIF":4.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11877937/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction Note: Ginsenoside Rg3 alleviates septic liver injury by regulating the lncRNA TUG1/miR-200c-3p/SIRT1 axis.","authors":"Pan Wu, Xiao Yu, Yue Peng, Qian-Lu Wang, Long-Tian Deng, Wei Xing","doi":"10.1186/s12950-025-00435-z","DOIUrl":"10.1186/s12950-025-00435-z","url":null,"abstract":"","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"22 1","pages":"10"},"PeriodicalIF":4.4,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11837600/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143450977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unfractionated heparin attenuated histone-induced pulmonary endothelial glycocalyx injury through Ang/Tie2 pathway.","authors":"Jia Yin, Yawen Chi, Danyan Liu, Xinghua Li, Xu Li","doi":"10.1186/s12950-025-00437-x","DOIUrl":"10.1186/s12950-025-00437-x","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to investigate the involvement of angiopoietin (Ang)/Tie2 pathway in mediating pulmonary endothelial glycocalyx injury in histone-induced acute lung injury in mice, and the protective mechanism of unfractionated heparin (UFH).</p><p><strong>Methods: </strong>Twenty-four male C57BL/6 mice (20-25 g), 8-12 weeks old, were randomly divided into control, histone, and histone + UFH groups. The histone (50 mg/kg) was administered via tail vein. UFH (400 U/kg) was administered 1 h after histone injection. The control group was administered by an equal amount of sterile saline solution. The lungs of all groups were harvested 4 h after the injection of histones or sterile saline.</p><p><strong>Results: </strong>UFH attenuated histone-induced lung histopathological changes and edema. UFH alleviated pulmonary endothelial injury and glycocalyx shedding by reducing histone-induced low expression of thrombomodulin (TM) and decreased lung syndecan-1 levels. UFH improved histone-induced low mRNA expression of TM, syndecan-1, Ang-1, Tie2 and high expression of heparinase (HPA), Ang-2.</p><p><strong>Conclusion: </strong>UFH may attenuate histone-induced lung injury and pulmonary endothelial glycocalyx degradation via the Ang/Tie2 pathway.</p>","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"22 1","pages":"9"},"PeriodicalIF":4.4,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143442997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Sodium pyruvate exerts protective effects against cigarette smoke extract-induced ferroptosis in alveolar and bronchial epithelial cells through the GPX4/Nrf2 axis.","authors":"Ziwen Zhao, Zhao Xu, Jingwen Chang, Liwei He, Zijin Zhang, Xiaoyu Song, Xianbang Hou, Fangtian Fan, Zhijun Jiang","doi":"10.1186/s12950-025-00436-y","DOIUrl":"10.1186/s12950-025-00436-y","url":null,"abstract":"","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"22 1","pages":"8"},"PeriodicalIF":4.4,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143442996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Auto-antibodies against carbonyl-modified vimentin in COPD: potential role as a biomarker.","authors":"L Heinemann, I Adcock, K F Chung, W Lollinga, M N Hylkema, A Papi, G Caramori, P A Kirkham","doi":"10.1186/s12950-025-00434-0","DOIUrl":"10.1186/s12950-025-00434-0","url":null,"abstract":"<p><p>COPD has many hallmarks of autoimmune dysfunction. Driving this autoimmune response are self-antigens, such as highly abundant structural proteins and cellular proteins, which can lead to the production of auto-antibodies. However, controversy surrounds the detection of some of these auto-antibodies as they have often been screened against native, unmodified proteins. Autoantigens arise as a result of a conformational change in the native protein exposing hidden epitopes or by the creation of neo-epitopes through chemical or enzymatic modifications, often caused by oxidative/carbonyl stress. In this study, we screened for auto-antibodies targeting key structural proteins modified by oxidative/carbonyl stress in peripheral blood from stable COPD patients versus control subjects using ELISA. We found an auto-antibody response against unmodified, carbonyl-modified and citrinylated vimentin, with the highest response observed against carbonyl-modified vimentin. Both the IgG and IgM antibody titres against carbonyl-modified were significantly increased in COPD patients compared to healthy non-smokers. Smokers also displayed increased antibody levels against carbonyl-modified vimentin, but only for the IgG isotype. Selectivity analysis indicated that 70% and 63% of COPD patients had higher IgM and IgG titres, respectively, compared to non-smokers. In contrast only 26% and 48% of smokers had higher IgM and IgG titres, respectively, than non-smokers. ROC analysis gave AUC values of 0.78 (p < 0.01) and 0.84 (p < 0.001) for IgM and IgG, respectively, for COPD versus non-smokers, which fell to 0.70 (p < 0.01) and 0.64 (NS), respectively, when asymptomatic smokers were included. No significant increase in antibody titre against carbonyl-modified elastin or collagen was observed in COPD patients or asymptomatic smokers. We conclude that IgM autoantibody responses against carbonyl modified vimentin could serve as a simple blood-based biomarker for COPD, reflecting the disease's pathophysiology, and could help in patient stratification and diagnosis.</p>","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"22 1","pages":"7"},"PeriodicalIF":4.4,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11817093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143400929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alpha-1 antitrypsin reduces inflammation and vasculopathy in mice with oxygen-induced retinopathy.","authors":"Varaporn Suphapimol, Yu-Han Liu, Sandro Prato, Alexander Karnowski, Charles Hardy, Adriana Baz Morelli, Abhirup Jayasimhan, Devy Deliyanti, Jennifer L Wilkinson-Berka","doi":"10.1186/s12950-025-00431-3","DOIUrl":"10.1186/s12950-025-00431-3","url":null,"abstract":"<p><strong>Background: </strong>Damage to the retinal vasculature is a major cause of vision loss and is influenced by a pro-inflammatory environment within retinal tissue. Alpha-1 antitrypsin (AAT) is a potent inhibitor of serine proteases and has anti-inflammatory properties. We hypothesised that AAT could reduce inflammation and vasculopathy in neovascular retinopathies including oxygen-induced retinopathy (OIR).</p><p><strong>Methods: </strong>Litters of C57BL/6J mice were randomised to develop OIR by exposure to high oxygen between postnatal days 7 to 12 resulting in vaso-obliteration (phase I OIR), and then room air from postnatal days 12 to 18 resulting in neovascularisation (phase II OIR). Control mice were exposed to room air. Separate cohorts of mice were administered control vehicle or human AAT (120 mg/kg) by intraperitoneal injection every second day in phase I or phase II OIR.</p><p><strong>Results: </strong>In phase I OIR, plasma levels of AAT were reduced compared to room air controls, and AAT treatment reduced vaso-obliteration. In phase II OIR, AAT treatment influenced inflammation by reducing the density of ionised calcium binding adaptor protein 1 + cells (microglia/macrophages) and modulating their cell process length and reducing mRNA levels of tumour necrosis factor and monocyte chemoattractant protein-1, but not interleukin-1b and interleukin-6 in retina. Furthermore, AAT treatment reduced retinal neovascularisation, gliosis, vascular endothelial growth factor mRNA and protein expression, and vascular leakage, compared to OIR controls.</p><p><strong>Conclusions: </strong>This research demonstrates the vasculo-protective actions of AAT, and thereby the potential of AAT as a therapeutic option for neovascular retinopathies.</p>","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"22 1","pages":"6"},"PeriodicalIF":4.4,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11817893/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143400907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Divergence in photoreceptor cell death and neuroinflammation in transvitreal and transscleral subretinal delivery in mice.","authors":"Daniel E Maidana, Sara Pastor Puente, Catherine Wang, Shivam Chandra, Lucia Gonzalez-Buendia, Eleftherios Paschalis Ilios, Andrius Kazlauskas, Demetrios G Vavvas","doi":"10.1186/s12950-025-00433-1","DOIUrl":"10.1186/s12950-025-00433-1","url":null,"abstract":"<p><p>Subretinal injections provide direct access to photoreceptors and RPE, which is crucial for the delivery of gene therapy and neuroprotective approaches. To access the subretinal space, transvitreal (TV) and transscleral (TS) subretinal injections have been widely used in humans and animal models. In this work, we investigated recent trends and outcomes of utilizing TV and TS subretinal models of retinal detachment (RD). A literature review revealed an increasing utilization of both models over the past two decades, with TS emerging as the predominant model since 2012. Subretinal injection in CX3CR1 + /GFP CCR2 + /RFP mice revealed early inflammatory responses, with TS injections inducing higher infiltration of CD11b + CCR2 + cells compared to TV. Further leukocyte immunophenotyping indicated divergent infiltration patterns, with the TS approach exhibiting higher proportions of neutrophils and macrophages/microglia-like cells, while the TV injections had higher CD45hi CD11b + Ly6G- Ly6C + infiltration. Notably, late-stage analysis demonstrates higher photoreceptor cell death in the TS approach, paralleled by increased subretinal infiltration of CD11b + cells. Both models showed significant reactive gliosis, suggesting comparable late-stage wound healing responses. These findings underscore the utility of these approaches for subretinal delivery, offering insights into their distinctive leukocyte infiltration and late-stage tissue responses.</p>","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"22 1","pages":"5"},"PeriodicalIF":4.4,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11806547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143371389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}