Soy isoflavones are natural tyrosine kinase inhibitors closely associated with decreased morbidity and mortality of various tumors.The activation of tyrosine kinases such as ERBB2 is the mechanism by which cholecystit...Soy isoflavones are natural tyrosine kinase inhibitors closely associated with decreased morbidity and mortality of various tumors.The activation of tyrosine kinases such as ERBB2 is the mechanism by which cholecystitis transforms into gallbladder cancer(GBC),therefore,it is important to investigate the relationship between long-term exposure to soy isoflavones and the occurrence and progression of GBC.This case-control study(n=85 pairs)found that the high level of plasma soy isoflavoneDgenistein(GEN)was associated with a lower risk of gallbladder cancer(≥326.00 ng/m L compared to≤19.30ng/m L,crude odds ratio 0.15,95%CI 0.04–0.59;P for trend=0.016),and that the level of GEN exposure negatively correlated with Ki67 expression in GBC tissue(n=85).Consistent with these results,the proliferation of GBC cells was inhibited in the long-term exposure models of GEN in vitro and in vivo.The long-term exposure to GEN reduced the tyrosine kinase activity of ERBB2 and impaired the function of the PTK6-AKT-GSK3βaxis,leading to downregulation of the MCM complex in GBC cells.In summary,long-term exposure to GEN associated with soy products intake might play a certain role in preventing GBC and even inhibiting the proliferation of GBC cells.展开更多
The RON receptor tyrosine kinase, a member of the MET proto-oncogene family, is a pathogenic factor im- plicated in tumor malignancy. Specifically, aberrations in RON signaling result in increased cancer cell growth, ...The RON receptor tyrosine kinase, a member of the MET proto-oncogene family, is a pathogenic factor im- plicated in tumor malignancy. Specifically, aberrations in RON signaling result in increased cancer cell growth, survival, invasion, angiogenesis, and drug resistance. Biochemical events such as ligand binding, receptor over- expression, generation of structure-defected variants, and point mutations in the kinase domain contribute to RON signaling activation. Recently, functional crosstalk between RON and signaling proteins such as MET and EFGR has emerged as an additional mechanism for RON activation, which is critical for tumorigenic develop- ment. The RON signaling crosstalk acts either as a regulatory feedback loop that strengthens or enhances tumor- igenic phenotype of cancer cells or serves as a signaling compensatory pathway providing a growth/survival ad- vantage for cancer cells to escape targeted therapy. Moreover, viral oncoproteins derived from Friend leukemia or Epstein-Barr viruses interact with RON to drive viral oncogenesis. In cancer cells, RON signaling is integrated into cellular signaling network essential for cancer cell growth and survival. These activities provide the mo- lecular basis of targeting RON for cancer treatment. In this review, we will discuss recent data that uncover the mechanisms of RON activation in cancer cells, review evidence of RON signaling crosstalk relevant to cancer malignancy, and emphasize the significance of the RON signaling addiction by cancer cells for tumor therapy. Understanding aberrant RON signaling will not only provide insight into the mechanisms of tumor pathogenesis, but also lead to the development of novel strategies for molecularly targeted cancer treatment.展开更多
Repetitive implant-related infections(IRIs)are devastating complications in orthopedic surgery,threatening implant survival and even the life of the host.Biofilms conceal bacterial-associated antigens(BAAs)and result ...Repetitive implant-related infections(IRIs)are devastating complications in orthopedic surgery,threatening implant survival and even the life of the host.Biofilms conceal bacterial-associated antigens(BAAs)and result in a"cold tumor"-like immune silent microenvironment,allowing the persistence of IRIs.To address this challenge,an iron-based covalent organic framed nanoadjuvant doped with curcumin and platinum(CFCP)was designed in the present study to achieve efficient treatment of IRIs by inducing a systemic immune response.Specifically,enhanced sonodynamic therapy(SDT)from CFCP combined with iron ion metabolic interference increased the release of bacterial-associated double-stranded DNA(dsDNA).Immunogenic dsDNA promoted dendritic cell(DC)maturation through activation of the stimulator of interferon gene(STING)and amplified the immune stimulation of neutrophils via interferon-β(IFN-β).At the same time,enhanced BAA presentation aroused humoral immunity in B and T cells,creating long-term resistance to repetitive infections.Encouragingly,CFCP served as neoadjuvant immunotherapy for sustained antibacterial protection on implants and was expected to guide clinical IRI treatment and relapse prevention.展开更多
Recently,nanovaccine-based immunotherapy has been robustly investigated due to its potential in governing the immune response and generating long-term protective immunity.However,the presentation of a tumor peptide-ma...Recently,nanovaccine-based immunotherapy has been robustly investigated due to its potential in governing the immune response and generating long-term protective immunity.However,the presentation of a tumor peptide-major histocompatibility complex to T lymphocytes is still a challenge that needs to be addressed for eliciting potent antitumor immunity.Type 1 conventional dendritic cell(cDC1)subset is of particular interest due to its pivotal contribution in the cross-presentation of exogenous antigens to CD8+T cells.Here,the DC-derived nanovaccine(denoted as Si9GM)selectively targets cDC1s with marginal loss of premature antigen release for effective stimulator of interferon genes(STING)-mediated antigen cross-presentation.Bone marrow dendritic cell(BMDC)-derived membranes,conjugated to cDC1-specific antibody(αCLEC9A)and binding to tumor peptide(OVA257-264),are coated onto dendrimer-like polyethylenimine(PEI)-grafted silica nanoparticles.Distinct molecular weight-cargos(αCLEC9A-OVA257-264 conjugates and 2′3′-cGAMP STING agonists)are loaded in hierarchical center-radial pores that enables lysosome escape for potent antigen-cross presentation and activates interferon type I,respectively.Impressively,Si9GM vaccination leads to the upregulation of cytotoxic T cells,a reduction in tumor regulatory T cells(Tregs),M1/M2 macrophage polarization,and immune response that synergizes with αPD-1 immune checkpoint blockade.This nanovaccine fulfills a dual role for both direct T cell activation as an artificial antigen-presenting cell and DC subset maturation,indicating its utility in clinical therapy and precision medicine.展开更多
Radiotherapy(RT)is a widely used cancer treatment,and the use of metal-based nano-radiotherapy sensitizers has shown promise in enhancing its efficacy.However,efficient accumulation and deep penetration of these sensi...Radiotherapy(RT)is a widely used cancer treatment,and the use of metal-based nano-radiotherapy sensitizers has shown promise in enhancing its efficacy.However,efficient accumulation and deep penetration of these sensitizers within tumors remain challenging.In this study,we present the development of bismuth/manganese biomineralized nanoparticles(Bi Mn/BSA)with multiple radiosensitizing mechanisms,including high atomic number element-mediated radiation capture,catalase-mimic oxygenation,and activation of the stimulator of interferon genes(STING)pathway.Significantly,we demonstrate that low-dose RT induces the recruitment of macrophages and subsequent upregulation of Matrix metalloproteinases(MMP)-2 and MMP-9 that degrade the extracellular matrix(ECM).This dynamic process facilitates the targeted delivery and deep penetration of Bi Mn/BSA nanoparticles within tumors,thereby enhancing the effectiveness of RT.By combining low-dose RT with Bi Mn/BSA nanoparticles,we achieved complete suppression of tumor growth in mice with excellent biocompatibility.This study provides a novel and clinically relevant strategy for targeted nanoparticle delivery to tumors,and establishes a safe and effective sequential radiotherapy approach for cancer treatment.These findings hold great promise for improving the outcomes of RT and advancing the field of nanomedicine in cancer therapy.展开更多
Background:Gram-positive bacteria stimulate Toll-like receptor(TLR)2 and then activate the pro-inflammatory nuclear factor-kappa B(NF-κB)pathway.As the human ocular surface is heavily colonised by gram-positive cocci...Background:Gram-positive bacteria stimulate Toll-like receptor(TLR)2 and then activate the pro-inflammatory nuclear factor-kappa B(NF-κB)pathway.As the human ocular surface is heavily colonised by gram-positive cocci bacteria,a balance of activation/repression of NF-κB target genes is essential to avoid uncontrolled infection or autoimmune-related inflammation.It is advantageous to test NF-κB targeting molecules in an ocular surface culture system that allows assessment of temporal NF-κB activation in a longitudinal fashion without destruction of cells.Such initial testing under standardised conditions should reduce the number of molecules that progress to further evaluation in animal models.This study aims to establish an in-vitro cell culture system to assess NF-κB activation in the context of ocular surface cells.Methods:NF-κB activity was evaluated through a secretory alkaline phosphatase reporter assay(SEAP).Immunoblots and immunofluorescence were used to examine IκBαphosphorylation and p65/p50 nuclear localization.Monocyte chemoattractant protein-1(MCP-1)transcripts were evaluated by real time PCR and protein levels were measured by ELISA.Results:NF-κB activity in HCE-T cells treated with TLR2 activator Pam3CSK4 was higher than control cells at both 6 and 24 h.Pam3CSK4-stimulated NF-κB activation was inhibited by IκK inhibitors,Wedelolactone and BMS-345541.In Pam3CSK4 treated cells,active NF-κB subunits p50 and p65 increased in cell nuclear fractions as early as 1.5 h.Although the level of total IκB-αremained constant,phospho-IκB-αincreased with treatment over time.In the culture media of Pam3CSK4-stimulated cells,MCP-1 protein level was increased,which was suppressed in the presence of IκK inhibitors.Conclusion:NF-κB pathway can be activated by the TLR2 ligand and inhibited by IκK inhibitors in the ocular surface cell culture system.This cell culture system may be used to evaluate TLR-related innate defences in ocular surface diseases.展开更多
The mesencephalic astrocyte-derived neurotrophic factor(MANF)has been recently identified as a neurotrophic factor,but its role in hepatic fibrosis is unknown.Here,we found that MANF was upregulated in the fibrotic li...The mesencephalic astrocyte-derived neurotrophic factor(MANF)has been recently identified as a neurotrophic factor,but its role in hepatic fibrosis is unknown.Here,we found that MANF was upregulated in the fibrotic liver tissues of the patients with chronic liver diseases and of mice treated with CCl4.MANF deficiency in either hepatocytes or hepatic mono-macrophages,particularly in hepatic mono-macrophages,clearly exacerbated hepatic fibrosis.Myeloid-specific MANF knockout increased the population of hepatic Ly6C^(high)macrophages and promoted HSCs activation.Furthermore,MANF-sufficient macrophages(from WT mice)transfusion ameliorated CCl4-induced hepatic fibrosis in myeloid cells-specific MANF knockout(MKO)mice.Mechanistically,MANF interacted with S100A8 to competitively block S100A8/A9 heterodimer formation and inhibited S100A8/A9-mediated TLR4-NF-κB signal activation.Pharmacologically,systemic administration of recombinant human MANF significantly alleviated CCl_(4)-induced hepatic fibrosis in both WT and hepatocytes-specific MANF knockout(HKO)mice.This study reveals a mechanism by which MANF targets S100A8/A9-TLR4 as a“brake”on the upstream of NF-κB pathway,which exerts an impact on macrophage differentiation and shed light on hepatic fibrosis treatment.展开更多
AIM: To investigate whether the complement system is involved in a murine model of oxygen-induced retinopathy(OIR).METHODS: Forty C57BL/6J newborn mice were divided randomly into OIR group and control group. OIR was i...AIM: To investigate whether the complement system is involved in a murine model of oxygen-induced retinopathy(OIR).METHODS: Forty C57BL/6J newborn mice were divided randomly into OIR group and control group. OIR was induced by exposing mice to 75% ±2% oxygen from postnatal 7d(P7) to P12 and then recovered in room air.For the control group, the litters were raised in room air.At the postnatal 17d(P17), gene expressions of the complement components of the classical pathway(CP),the mannose-binding lectin(MBL) pathway and the alternative pathway(AP) in the retina were determined by quantitative real-time polymerase chain reaction(RT-PCR). Retinal protein expressions of the key components in the CP were examined by Western blotting.· RESULTS: Whole mounted retina in the OIR mice showed area of central hypoperfusion in both superficial and deep layers and neovascular tufts in the periphery.The expressions of C1 qb and C4 b genes in the OIR retina were significantly higher than those of the controls. The expression of retinal complement factor B(CFB) gene in OIR mice was significantly lower than those of the controls. However, the expressions of C3 and complement factor H(CFH) genes were higher. The protein synthesis of the key components involved in the CP(C1q, C4 and C3) were also significantly higher in OIR mouse retina. Although MBL-associated serine protease 1(MASP1) and MASP2 were detected in both the OIR and the control groups, the expressions were weak and the difference between the two groups was not significant.CONCLUSION: Our data suggest that the complement system CP is activated during the pathogenesis of murine model of OIR.展开更多
基金supported by the National Natural Science Foundation of China(2019XH004,81874181,82073206,21705108,and 81773043)the Emerging Frontier Program of Hospital Development Centre(SHDC12018107)+4 种基金the Key Program of Shanghai Science and Technology Commission(YDZX20193100004049)the State Key Laboratory of Oncogenes and Related Genes(KF2120)the National Key Research and Development Program of China(2021YFE0203300)the Shuguang Program of Shanghai Education Development Foundation and Shanghai Municipal Education Commission(20SG14)he Program of Shanghai Academic Research Leader(19XD1422700)。
文摘Soy isoflavones are natural tyrosine kinase inhibitors closely associated with decreased morbidity and mortality of various tumors.The activation of tyrosine kinases such as ERBB2 is the mechanism by which cholecystitis transforms into gallbladder cancer(GBC),therefore,it is important to investigate the relationship between long-term exposure to soy isoflavones and the occurrence and progression of GBC.This case-control study(n=85 pairs)found that the high level of plasma soy isoflavoneDgenistein(GEN)was associated with a lower risk of gallbladder cancer(≥326.00 ng/m L compared to≤19.30ng/m L,crude odds ratio 0.15,95%CI 0.04–0.59;P for trend=0.016),and that the level of GEN exposure negatively correlated with Ki67 expression in GBC tissue(n=85).Consistent with these results,the proliferation of GBC cells was inhibited in the long-term exposure models of GEN in vitro and in vivo.The long-term exposure to GEN reduced the tyrosine kinase activity of ERBB2 and impaired the function of the PTK6-AKT-GSK3βaxis,leading to downregulation of the MCM complex in GBC cells.In summary,long-term exposure to GEN associated with soy products intake might play a certain role in preventing GBC and even inhibiting the proliferation of GBC cells.
基金supported in part by National Institutes of Health grantR01 CA91980 (MHW)a grant from the Amarillo Area Foundation(MHW)supported by NIH grants R01 CA112029 and CA121211
文摘The RON receptor tyrosine kinase, a member of the MET proto-oncogene family, is a pathogenic factor im- plicated in tumor malignancy. Specifically, aberrations in RON signaling result in increased cancer cell growth, survival, invasion, angiogenesis, and drug resistance. Biochemical events such as ligand binding, receptor over- expression, generation of structure-defected variants, and point mutations in the kinase domain contribute to RON signaling activation. Recently, functional crosstalk between RON and signaling proteins such as MET and EFGR has emerged as an additional mechanism for RON activation, which is critical for tumorigenic develop- ment. The RON signaling crosstalk acts either as a regulatory feedback loop that strengthens or enhances tumor- igenic phenotype of cancer cells or serves as a signaling compensatory pathway providing a growth/survival ad- vantage for cancer cells to escape targeted therapy. Moreover, viral oncoproteins derived from Friend leukemia or Epstein-Barr viruses interact with RON to drive viral oncogenesis. In cancer cells, RON signaling is integrated into cellular signaling network essential for cancer cell growth and survival. These activities provide the mo- lecular basis of targeting RON for cancer treatment. In this review, we will discuss recent data that uncover the mechanisms of RON activation in cancer cells, review evidence of RON signaling crosstalk relevant to cancer malignancy, and emphasize the significance of the RON signaling addiction by cancer cells for tumor therapy. Understanding aberrant RON signaling will not only provide insight into the mechanisms of tumor pathogenesis, but also lead to the development of novel strategies for molecularly targeted cancer treatment.
基金supported by the National Natural Science Foundation of China(82272512,82102586)the Natural Science Foundation of Anhui Province,Distinguishing Youth Project(2108085J40)+1 种基金Anhui Provincial Scientific Research Compilation Project(2022AH051251,2022AH010076)Research Funds of Centre for Leading Medicine and Advanced Technologies of IHM(2023IHM01070,2023IHM01074).
文摘Repetitive implant-related infections(IRIs)are devastating complications in orthopedic surgery,threatening implant survival and even the life of the host.Biofilms conceal bacterial-associated antigens(BAAs)and result in a"cold tumor"-like immune silent microenvironment,allowing the persistence of IRIs.To address this challenge,an iron-based covalent organic framed nanoadjuvant doped with curcumin and platinum(CFCP)was designed in the present study to achieve efficient treatment of IRIs by inducing a systemic immune response.Specifically,enhanced sonodynamic therapy(SDT)from CFCP combined with iron ion metabolic interference increased the release of bacterial-associated double-stranded DNA(dsDNA).Immunogenic dsDNA promoted dendritic cell(DC)maturation through activation of the stimulator of interferon gene(STING)and amplified the immune stimulation of neutrophils via interferon-β(IFN-β).At the same time,enhanced BAA presentation aroused humoral immunity in B and T cells,creating long-term resistance to repetitive infections.Encouragingly,CFCP served as neoadjuvant immunotherapy for sustained antibacterial protection on implants and was expected to guide clinical IRI treatment and relapse prevention.
基金supported by a National Research Foundation of Korea(NRF)grant funded by the Korean government(MSIT,No.RS-2024-00352440 and No.NRF-2019R1A5A2027340).
文摘Recently,nanovaccine-based immunotherapy has been robustly investigated due to its potential in governing the immune response and generating long-term protective immunity.However,the presentation of a tumor peptide-major histocompatibility complex to T lymphocytes is still a challenge that needs to be addressed for eliciting potent antitumor immunity.Type 1 conventional dendritic cell(cDC1)subset is of particular interest due to its pivotal contribution in the cross-presentation of exogenous antigens to CD8+T cells.Here,the DC-derived nanovaccine(denoted as Si9GM)selectively targets cDC1s with marginal loss of premature antigen release for effective stimulator of interferon genes(STING)-mediated antigen cross-presentation.Bone marrow dendritic cell(BMDC)-derived membranes,conjugated to cDC1-specific antibody(αCLEC9A)and binding to tumor peptide(OVA257-264),are coated onto dendrimer-like polyethylenimine(PEI)-grafted silica nanoparticles.Distinct molecular weight-cargos(αCLEC9A-OVA257-264 conjugates and 2′3′-cGAMP STING agonists)are loaded in hierarchical center-radial pores that enables lysosome escape for potent antigen-cross presentation and activates interferon type I,respectively.Impressively,Si9GM vaccination leads to the upregulation of cytotoxic T cells,a reduction in tumor regulatory T cells(Tregs),M1/M2 macrophage polarization,and immune response that synergizes with αPD-1 immune checkpoint blockade.This nanovaccine fulfills a dual role for both direct T cell activation as an artificial antigen-presenting cell and DC subset maturation,indicating its utility in clinical therapy and precision medicine.
基金the National Natural Science Foundation of China(Nos.81771827,82071986,82372072)the Key Research and Development Program of Hunan Province(No.2022SK2025)+5 种基金the Natural Science Foundation of Hunan Province(Nos.2023JJ40966,2021JJ20084)the Science and Technology Program of Hunan Province(Nos.2021RC4017,2021RC3020)the Youth Science Foundation of Xiangya Hospital(No.2022Q13)the Central South University Frontier Cross-disciplinary Project(No.2023QYJC021)the China Postdoctoral Science Foundation(No.2023M733954)the National Postdoctoral Program for Innovative Talents(No.BX20230432)。
文摘Radiotherapy(RT)is a widely used cancer treatment,and the use of metal-based nano-radiotherapy sensitizers has shown promise in enhancing its efficacy.However,efficient accumulation and deep penetration of these sensitizers within tumors remain challenging.In this study,we present the development of bismuth/manganese biomineralized nanoparticles(Bi Mn/BSA)with multiple radiosensitizing mechanisms,including high atomic number element-mediated radiation capture,catalase-mimic oxygenation,and activation of the stimulator of interferon genes(STING)pathway.Significantly,we demonstrate that low-dose RT induces the recruitment of macrophages and subsequent upregulation of Matrix metalloproteinases(MMP)-2 and MMP-9 that degrade the extracellular matrix(ECM).This dynamic process facilitates the targeted delivery and deep penetration of Bi Mn/BSA nanoparticles within tumors,thereby enhancing the effectiveness of RT.By combining low-dose RT with Bi Mn/BSA nanoparticles,we achieved complete suppression of tumor growth in mice with excellent biocompatibility.This study provides a novel and clinically relevant strategy for targeted nanoparticle delivery to tumors,and establishes a safe and effective sequential radiotherapy approach for cancer treatment.These findings hold great promise for improving the outcomes of RT and advancing the field of nanomedicine in cancer therapy.
基金supported by the Singapore National Research Foundation(NMRC/CSA/045/2012)administered by the Singapore Ministry of Health’s National Medical Research Council.
文摘Background:Gram-positive bacteria stimulate Toll-like receptor(TLR)2 and then activate the pro-inflammatory nuclear factor-kappa B(NF-κB)pathway.As the human ocular surface is heavily colonised by gram-positive cocci bacteria,a balance of activation/repression of NF-κB target genes is essential to avoid uncontrolled infection or autoimmune-related inflammation.It is advantageous to test NF-κB targeting molecules in an ocular surface culture system that allows assessment of temporal NF-κB activation in a longitudinal fashion without destruction of cells.Such initial testing under standardised conditions should reduce the number of molecules that progress to further evaluation in animal models.This study aims to establish an in-vitro cell culture system to assess NF-κB activation in the context of ocular surface cells.Methods:NF-κB activity was evaluated through a secretory alkaline phosphatase reporter assay(SEAP).Immunoblots and immunofluorescence were used to examine IκBαphosphorylation and p65/p50 nuclear localization.Monocyte chemoattractant protein-1(MCP-1)transcripts were evaluated by real time PCR and protein levels were measured by ELISA.Results:NF-κB activity in HCE-T cells treated with TLR2 activator Pam3CSK4 was higher than control cells at both 6 and 24 h.Pam3CSK4-stimulated NF-κB activation was inhibited by IκK inhibitors,Wedelolactone and BMS-345541.In Pam3CSK4 treated cells,active NF-κB subunits p50 and p65 increased in cell nuclear fractions as early as 1.5 h.Although the level of total IκB-αremained constant,phospho-IκB-αincreased with treatment over time.In the culture media of Pam3CSK4-stimulated cells,MCP-1 protein level was increased,which was suppressed in the presence of IκK inhibitors.Conclusion:NF-κB pathway can be activated by the TLR2 ligand and inhibited by IκK inhibitors in the ocular surface cell culture system.This cell culture system may be used to evaluate TLR-related innate defences in ocular surface diseases.
基金supported by the National Natural Science Foundation of China(81973336)the Joint Fund of the National Natural Science Foundation of China(U21A20345)。
文摘The mesencephalic astrocyte-derived neurotrophic factor(MANF)has been recently identified as a neurotrophic factor,but its role in hepatic fibrosis is unknown.Here,we found that MANF was upregulated in the fibrotic liver tissues of the patients with chronic liver diseases and of mice treated with CCl4.MANF deficiency in either hepatocytes or hepatic mono-macrophages,particularly in hepatic mono-macrophages,clearly exacerbated hepatic fibrosis.Myeloid-specific MANF knockout increased the population of hepatic Ly6C^(high)macrophages and promoted HSCs activation.Furthermore,MANF-sufficient macrophages(from WT mice)transfusion ameliorated CCl4-induced hepatic fibrosis in myeloid cells-specific MANF knockout(MKO)mice.Mechanistically,MANF interacted with S100A8 to competitively block S100A8/A9 heterodimer formation and inhibited S100A8/A9-mediated TLR4-NF-κB signal activation.Pharmacologically,systemic administration of recombinant human MANF significantly alleviated CCl_(4)-induced hepatic fibrosis in both WT and hepatocytes-specific MANF knockout(HKO)mice.This study reveals a mechanism by which MANF targets S100A8/A9-TLR4 as a“brake”on the upstream of NF-κB pathway,which exerts an impact on macrophage differentiation and shed light on hepatic fibrosis treatment.
基金Supported partially by National Natural Science Foundation of China(No.81271033,81470621)
文摘AIM: To investigate whether the complement system is involved in a murine model of oxygen-induced retinopathy(OIR).METHODS: Forty C57BL/6J newborn mice were divided randomly into OIR group and control group. OIR was induced by exposing mice to 75% ±2% oxygen from postnatal 7d(P7) to P12 and then recovered in room air.For the control group, the litters were raised in room air.At the postnatal 17d(P17), gene expressions of the complement components of the classical pathway(CP),the mannose-binding lectin(MBL) pathway and the alternative pathway(AP) in the retina were determined by quantitative real-time polymerase chain reaction(RT-PCR). Retinal protein expressions of the key components in the CP were examined by Western blotting.· RESULTS: Whole mounted retina in the OIR mice showed area of central hypoperfusion in both superficial and deep layers and neovascular tufts in the periphery.The expressions of C1 qb and C4 b genes in the OIR retina were significantly higher than those of the controls. The expression of retinal complement factor B(CFB) gene in OIR mice was significantly lower than those of the controls. However, the expressions of C3 and complement factor H(CFH) genes were higher. The protein synthesis of the key components involved in the CP(C1q, C4 and C3) were also significantly higher in OIR mouse retina. Although MBL-associated serine protease 1(MASP1) and MASP2 were detected in both the OIR and the control groups, the expressions were weak and the difference between the two groups was not significant.CONCLUSION: Our data suggest that the complement system CP is activated during the pathogenesis of murine model of OIR.