Nlrp3 inflammasome activation in early diabetic retinopathy
早期糖尿病视网膜病变中 Nlrp3 炎性体激活
基本信息
- 批准号:10626060
- 负责人:
- 金额:$ 47.28万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-09-01 至 2025-05-31
- 项目状态:未结题
- 来源:
- 关键词:AblationAcuteAddressAffectAge related macular degenerationAlzheimer&aposs DiseaseAnimal ModelApoptosisAtherosclerosisBlindnessBlood VesselsBlood-Retinal BarrierCASP1 geneCell DeathCell modelCellsChronicClinicalComplexComplicationDefectDiabetes MellitusDiabetic RetinopathyDiabetic mouseDimensionsDiseaseDoseExhibitsEye diseasesFunctional disorderGeneticGenetic RecombinationGlucoseGoalsHemorrhageHumanImmuneImmune signalingIn SituIndividualInflammasomeInflammatoryInsulin-Dependent Diabetes MellitusInterventionKnock-outKnowledgeLeukostasisLyticMeasuresMedicalMethodsMicrovascular DysfunctionMitochondriaModelingMolecular Biology TechniquesMusMyeloid CellsNerve DegenerationNeurogliaNeuronsNonesterified Fatty AcidsPathogenesisPathologicPathologic ProcessesPathologyPathway interactionsPatientsPeptide HydrolasesPersonsPhenotypePre-Clinical ModelProcessProductionReactive Oxygen SpeciesReporter GenesResearchRetinaRetinal DiseasesRheumatoid ArthritisRiskRoleSamplingSignal TransductionSourceStreptozocinStreptozocin DiabetesTestingTherapeuticTransgenic OrganismsVisioncell typecytokinediabetes managementdiabeticefficacy evaluationefficacy testingendothelial dysfunctioninhibitorinsightislet amyloid polypeptidemouse modelneuralneural modelneurovascularpathogenpharmacologicpre-clinicalpreventpromoterrecruitresponsestressor
项目摘要
Abstract/Summary
Hallmark pathologic processes of diabetic retinopathy (DR) include neural and glial dysfunction, recruitment of
inflammatory cells, endothelial dysfunction, vascular occlusion, and loss of the blood retinal barrier.
Inflammasomes are innate immune signaling platforms implicated in acute responses to foreign pathogens as
well as numerous chronic neurodegenerative- and inflammatory-related diseases. Inflammasome blockade is
being explored for multiple complex neurovascular conditions including Alzheimer's disease, atherosclerosis,
age-related macular degeneration, and rheumatoid arthritis. Clinical and preclinical evidence suggest that
inflammasome activity may also contribute to pathological hallmarks of DR by promoting production of
inflammatory cytokines, leukostasis, and loss of microvascular integrity. Despite this evidence, major gaps in
knowledge persist with respect to the timing, cellular sources, and pathological implications of inflammasome
activation in the context of diabetic retinopathy. The overall hypothesis of this proposal is that NLRP3
inflammasome activation in circulating immune cells and resident neuroglia drives neuronal and microvascular
dysfunction in diabetic retinopathy. We will test this hypothesis in three specific aims: 1) We seek to identify cell
types that exhibit inflammasome activation and the timing thereof in an animal model of type 1 diabetes; 2) We
seek to determine the contribution of core inflammasome constituents to hallmark pathological phenotypes in
animal models of retinal pathologies due to diabetes. To accomplish this, we will utilize global and cell-specific
genetic knockouts of inflammasome constituents in models of diabetes; 3) We seek to test the efficacy of
pharmacological inflammasome inhibitors in preclinical models of neural, immune, and vascular defects due to
diabetes. Collectively, these thematically related, but independent aims will establish the contribution of
inflammasome in pathological processes of diabetes in the retina. These studies may thereby open new
interventional avenues for this prevalent blinding condition.
摘要/总结
糖尿病视网膜病变 (DR) 的标志性病理过程包括神经和神经胶质功能障碍、
炎症细胞、内皮功能障碍、血管闭塞和血视网膜屏障丧失。
炎症小体是先天免疫信号平台,与对外来病原体的急性反应有关
以及许多慢性神经退行性和炎症相关疾病。炎症小体阻断是
正在探索多种复杂的神经血管疾病,包括阿尔茨海默病、动脉粥样硬化、
年龄相关性黄斑变性和类风湿性关节炎。临床和临床前证据表明
炎症小体活动也可能通过促进产生
炎症细胞因子、白细胞停滞和微血管完整性丧失。尽管有这些证据,但在
关于炎症小体的时间、细胞来源和病理影响的知识仍然存在
糖尿病视网膜病变背景下的激活。该提案的总体假设是 NLRP3
循环免疫细胞和驻留神经胶质细胞中的炎症小体激活驱动神经元和微血管
糖尿病视网膜病变的功能障碍。我们将在三个具体目标中检验这一假设:1)我们寻求识别细胞
在 1 型糖尿病动物模型中表现出炎症体激活的类型及其时间; 2)我们
寻求确定核心炎性体成分对标志性病理表型的贡献
糖尿病引起的视网膜病变的动物模型。为了实现这一目标,我们将利用全局和细胞特定的
糖尿病模型中炎症小体成分的基因敲除; 3)我们试图测试其功效
药理学炎症小体抑制剂在神经、免疫和血管缺陷临床前模型中的应用
糖尿病。总的来说,这些主题相关但独立的目标将建立以下贡献:
视网膜糖尿病病理过程中的炎症小体。这些研究可能因此开启新的
针对这种普遍致盲情况的介入途径。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Jayakrishna Ambati其他文献
Jayakrishna Ambati的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Jayakrishna Ambati', 18)}}的其他基金
Cytosolic SINE retrotransposable element cDNA and mitochondrial DNA in aging retina
衰老视网膜中的胞质 SINE 逆转录转座元件 cDNA 和线粒体 DNA
- 批准号:
10722062 - 财政年份:2023
- 资助金额:
$ 47.28万 - 项目类别:
Defining the role of SINE retrotransposons and inflammasome activation in Alzheimer's disease
定义 SINE 逆转录转座子和炎症小体激活在阿尔茨海默病中的作用
- 批准号:
10696066 - 财政年份:2022
- 资助金额:
$ 47.28万 - 项目类别:
Defining the role of SINE retrotransposons and inflammasome activation in Alzheimer's disease
定义 SINE 逆转录转座子和炎症小体激活在阿尔茨海默病中的作用
- 批准号:
10517678 - 财政年份:2022
- 资助金额:
$ 47.28万 - 项目类别:
Nlrp3 inflammasome activation in early diabetic retinopathy - Administrative Supplement ERG Request
早期糖尿病视网膜病变中 Nlrp3 炎症小体激活 - 行政补充 ERG 请求
- 批准号:
10643583 - 财政年份:2020
- 资助金额:
$ 47.28万 - 项目类别:
Inflammasome-based Alzheimer's disease therapy in the context of diabetes
糖尿病背景下基于炎症小体的阿尔茨海默病治疗
- 批准号:
10287353 - 财政年份:2020
- 资助金额:
$ 47.28万 - 项目类别:
Nlrp3 inflammasome activation in early diabetic retinopathy
早期糖尿病视网膜病变中 Nlrp3 炎性体激活
- 批准号:
10414049 - 财政年份:2020
- 资助金额:
$ 47.28万 - 项目类别:
Visual system and cognitive biology in normal animals versus in an animal model of Alzheimer's disease with or without diabetes treated with solo or dual inflammasome inhibitors
正常动物的视觉系统和认知生物学与单独或双重炎性体抑制剂治疗的患有或不患有糖尿病的阿尔茨海默病动物模型的比较
- 批准号:
10712956 - 财政年份:2020
- 资助金额:
$ 47.28万 - 项目类别:
Non-canonical inflammasome in activation in RPE degeneration
RPE 变性中激活的非典型炎症小体
- 批准号:
10338080 - 财政年份:2019
- 资助金额:
$ 47.28万 - 项目类别:
Antigen-independent suppression of ocular angiogenesis via the Fc receptor
通过 Fc 受体对眼部血管生成进行抗原非依赖性抑制
- 批准号:
10003425 - 财政年份:2018
- 资助金额:
$ 47.28万 - 项目类别:
Antigen-independent suppression of ocular angiogenesis via the Fc receptor
通过 Fc 受体对眼部血管生成进行抗原非依赖性抑制
- 批准号:
9765313 - 财政年份:2018
- 资助金额:
$ 47.28万 - 项目类别:
相似海外基金
Transcriptional assessment of haematopoietic differentiation to risk-stratify acute lymphoblastic leukaemia
造血分化的转录评估对急性淋巴细胞白血病的风险分层
- 批准号:
MR/Y009568/1 - 财政年份:2024
- 资助金额:
$ 47.28万 - 项目类别:
Fellowship
Combining two unique AI platforms for the discovery of novel genetic therapeutic targets & preclinical validation of synthetic biomolecules to treat Acute myeloid leukaemia (AML).
结合两个独特的人工智能平台来发现新的基因治疗靶点
- 批准号:
10090332 - 财政年份:2024
- 资助金额:
$ 47.28万 - 项目类别:
Collaborative R&D
Acute senescence: a novel host defence counteracting typhoidal Salmonella
急性衰老:对抗伤寒沙门氏菌的新型宿主防御
- 批准号:
MR/X02329X/1 - 财政年份:2024
- 资助金额:
$ 47.28万 - 项目类别:
Fellowship
Cellular Neuroinflammation in Acute Brain Injury
急性脑损伤中的细胞神经炎症
- 批准号:
MR/X021882/1 - 财政年份:2024
- 资助金额:
$ 47.28万 - 项目类别:
Research Grant
STTR Phase I: Non-invasive focused ultrasound treatment to modulate the immune system for acute and chronic kidney rejection
STTR 第一期:非侵入性聚焦超声治疗调节免疫系统以治疗急性和慢性肾排斥
- 批准号:
2312694 - 财政年份:2024
- 资助金额:
$ 47.28万 - 项目类别:
Standard Grant
Combining Mechanistic Modelling with Machine Learning for Diagnosis of Acute Respiratory Distress Syndrome
机械建模与机器学习相结合诊断急性呼吸窘迫综合征
- 批准号:
EP/Y003527/1 - 财政年份:2024
- 资助金额:
$ 47.28万 - 项目类别:
Research Grant
FITEAML: Functional Interrogation of Transposable Elements in Acute Myeloid Leukaemia
FITEAML:急性髓系白血病转座元件的功能研究
- 批准号:
EP/Y030338/1 - 财政年份:2024
- 资助金额:
$ 47.28万 - 项目类别:
Research Grant
KAT2A PROTACs targetting the differentiation of blasts and leukemic stem cells for the treatment of Acute Myeloid Leukaemia
KAT2A PROTAC 靶向原始细胞和白血病干细胞的分化,用于治疗急性髓系白血病
- 批准号:
MR/X029557/1 - 财政年份:2024
- 资助金额:
$ 47.28万 - 项目类别:
Research Grant
ロボット支援肝切除術は真に低侵襲なのか?acute phaseに着目して
机器人辅助肝切除术真的是微创吗?
- 批准号:
24K19395 - 财政年份:2024
- 资助金额:
$ 47.28万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Acute human gingivitis systems biology
人类急性牙龈炎系统生物学
- 批准号:
484000 - 财政年份:2023
- 资助金额:
$ 47.28万 - 项目类别:
Operating Grants