A new class of wet AMD therapeutics
新型湿性 AMD 疗法
基本信息
- 批准号:10659582
- 负责人:
- 金额:$ 39.13万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-09-30 至 2027-06-30
- 项目状态:未结题
- 来源:
- 关键词:AblationAcetatesAddressAdoptive TransferAffectAgeAge related macular degenerationAngiogenesis InhibitorsAnimalsAnti-Inflammatory AgentsBasic ScienceBenchmarkingBindingBiological AssayBlindnessCadaverCell RespirationCell SeparationCellsChoroidChoroidal NeovascularizationCirculationClinical ResearchCoculture TechniquesComplicationCoupledDataDiseaseElderlyEndothelial CellsExudative age-related macular degenerationEyeFlow CytometryFoundationsG-Protein-Coupled ReceptorsGenesGenetic PolymorphismGlycolysisImmuneIn VitroIncidenceInfiltrationInflammationInflammatoryInterventionInvadedKetone BodiesKetonesKetosesKetosisKineticsKnockout MiceKnowledgeLasersLeftLegal BlindnessLesionLinkLiverMacrophageMetabolicMetabolismMicrogliaModelingNatural ImmunityPathologicPathologyPatientsPeripheralPhenotypePlayPopulationProcessRetinaRiskRoleSeveritiesTestingTherapeuticTherapeutic EffectTreatment EfficacyVLDL receptorVisionWorkangiogenesisbeta-Hydroxybutyratebevacizumabcell typedietarygenome wide association studyimmunoregulationlegally blindmaculamonocyteneovascularizationneutrophiloxidized lipidparacrineprogramsreceptorrecruitsingle-cell RNA sequencingstandard of caretherapy development
项目摘要
ABSTRACT
Advanced neovascular age-related macular degeneration (AMD) is characterized by choroidal
neovascularization (CNV), in which neovessels originating from the choroid invade the macula. CNV causes
permanent central blindness if left untreated and is the most sight-threatening pathology of AMD. The present
application will investigate the efficacy and regulatory mechanisms for a new class of CNV therapeutics. We
have identified in our preliminary data that ketone bodies suppress CNV and hypothesize that this effect is
regulated by macrophage and/or microglia reprogramming, which results in protective inflammation and/or
suppression of pathological inflammation. We will refute or validate this hypothesis in three Specific Aims. In
Aim 1, we will determine the therapeutic effects of ketone metabolites and their potential synergistic effect with
anti-VEGF therapies, the current standard of care for CNV. We will also determine whether the anti-angiogenic
effects of ketone metabolites are regulated by direct effects on endothelial cells or ketone-induced immune cell
phenotypic changes using co-culture models. In Aim 2, we will identify whether ketone bodies suppress CNV
via microglia, macrophages recruited from the circulation, or both. In Aim 3, we will determine the role of the
ketone body receptor, G Protein-coupled receptor 109a (Gpr109a) in phenotypic reprogramming of specific
immune cell subpopulations.
摘要
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)
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Elizabeth Moran其他文献
Elizabeth Moran的其他文献
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{{ truncateString('Elizabeth Moran', 18)}}的其他基金
The p270 SWI/SNF subunit as a potential Wilms' tumor susceptibility gene
p270 SWI/SNF 亚基作为潜在的维尔姆斯肿瘤易感基因
- 批准号:
7637741 - 财政年份:2008
- 资助金额:
$ 39.13万 - 项目类别:
The p270 SWI/SNF subunit as a potential Wilms' tumor susceptibility gene
p270 SWI/SNF 亚基作为潜在的维尔姆斯肿瘤易感基因
- 批准号:
7390516 - 财政年份:2008
- 资助金额:
$ 39.13万 - 项目类别:
SWI/SNF-related complex in osteoblast differentiation
成骨细胞分化中 SWI/SNF 相关复合物
- 批准号:
7189833 - 财政年份:2006
- 资助金额:
$ 39.13万 - 项目类别:
SWI/SNF-related complex in osteoblast differentiation
成骨细胞分化中 SWI/SNF 相关复合物
- 批准号:
7668391 - 财政年份:2006
- 资助金额:
$ 39.13万 - 项目类别:
SWI/SNF-related complex in osteoblast differentiation
成骨细胞分化中 SWI/SNF 相关复合物
- 批准号:
7105890 - 财政年份:2006
- 资助金额:
$ 39.13万 - 项目类别:
SWI/SNF-related complex in osteoblast differentiation
成骨细胞分化中 SWI/SNF 相关复合物
- 批准号:
7493385 - 财政年份:2006
- 资助金额:
$ 39.13万 - 项目类别:
CELL GROWTH CONTROL FUNCTIONS OF THE E1A ONCOGENE
E1A 癌基因的细胞生长控制功能
- 批准号:
2096547 - 财政年份:1991
- 资助金额:
$ 39.13万 - 项目类别:
PROTEIN INTERACTIONS AND REPRESSION FUNCTION OF THE E1A
E1A 的蛋白质相互作用和抑制功能
- 批准号:
3198310 - 财政年份:1991
- 资助金额:
$ 39.13万 - 项目类别:
PROTEIN INTERACTIONS AND REPRESSION FUNCTION OF E1A
E1A 的蛋白质相互作用和抑制功能
- 批准号:
6172484 - 财政年份:1991
- 资助金额:
$ 39.13万 - 项目类别:
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