Identification of novel therapeutic targets for age-related macular degeneration via a combined tissue engineering and systems biology approach
通过组织工程和系统生物学相结合的方法确定年龄相关性黄斑变性的新治疗靶点
基本信息
- 批准号:9181720
- 负责人:
- 金额:$ 24.29万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-08-01 至 2018-07-31
- 项目状态:已结题
- 来源:
- 关键词:3-DimensionalAcuteAddressAffectAge related macular degenerationAnatomyAngiogenesis InhibitorsAngiogenic FactorBiologicalBiologyBlindnessBloodBlood VesselsBruch&aposs basal membrane structureCell Surface ReceptorsChoroidChoroidal NeovascularizationCoculture TechniquesCollagenComplexComputer SimulationDevelopmentDiffusionDiseaseDrug usageElderlyElementsEndothelial CellsEngineeringEnvironmentEpithelialExperimental ModelsExtracellular MatrixEyeFDA approvedFunctional disorderGoldGrowthIn VitroIndividualLeadLigandsLiquid substanceLucentisModelingMolecularOutcomePatientsPharmaceutical PreparationsPhenotypePhosphorylationProcessPropertyReceptor ActivationRetinaRetinalRetinal PigmentsRiskRoleStagingStructureStructure of retinal pigment epitheliumSystemSystems BiologyTestingTimeTissue EngineeringTissuesTubular formationVascular Endothelial Growth FactorsWorkalternative treatmentangiogenesiscosteffective therapyexperienceglycationin vitro Modelinnovationinsightneovascularizationnew therapeutic targetnovelnovel therapeutic interventionnovel therapeuticsranibizumabreceptorresearch studyresponsetreatment strategy
项目摘要
PROJECT SUMMARY
Age-related macular degeneration (AMD) is the leading cause of blindness in the developed world, and results
from inappropriate angiogenesis in the eye. As a result of this mechanism, anti-angiogenic drugs such as anti-
vascular endothelial growth factor (VEGF) agents have become the preferred treatment for late-stage, or `wet',
AMD. However, these drugs are accompanied by serious risks as they are injected repeatedly into the eye and
over 50% of patients still experience vision loss. Unfortunately, the development of more effective therapies
has been hampered by limited insight into the molecular mechanisms that promote angiogenesis in the retina.
We hypothesize that the combined changes in the extracellular matrix (ECM) and retinal pigment epithelial
(RPE) phenotype control angiogenesis in wet AMD. To test this, we propose to develop a tissue-engineered
system that mimics several features of outer retinal anatomy and to then characterize angiogenesis in
response to AMD-like changes to these features. This novel 3-D platform will allow us to uniquely address
specific questions about retinal biology, yield information about the relative influences of retinal properties in
regulating angiogenesis, and ultimately identify and screen new therapies for wet AMD.
Aim 1: Create a tissue-engineered retinal environment to characterize the relative influences of AMD-
mimicking changes on angiogenesis. We will develop a novel 3-D tissue-engineered system simulating key
elements of the retinal anatomy. This system will be used to examine angiogenesis by endothelial cells (ECs)
in the context of changes in the retinal microenvironment that mimic changes observed in wet AMD.
Aim 2: Using a systems biology analysis, identify alternative targets or stage-specific treatments to
regulate angiogenesis in AMD. We will utilize our tissue-engineered model to examine receptor activation on
the ECs in response to angiogenic ligands secreted by RPE cells across different stages of angiogenesis. We
will then use these experiments to construct a predictive computational model that will enable identification of
individual (or combined) soluble factors that most strongly promote angiogenesis at various stages of disease.
Via in silico perturbations, we will predict outcomes for inhibiting these factors/receptors, and then test these
new inhibition strategies in our in vitro experimental model.
The outcomes of this work will be: 1) creation of a sophisticated in vitro platform for characterizing the
pathophysiology of wet AMD and relative contributions of microenvironmental factors in this process, 2)
identification of novel targets and/or stage-specific treatments for wet AMD.
项目总结
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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KRISTYN S MASTERS其他文献
KRISTYN S MASTERS的其他文献
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{{ truncateString('KRISTYN S MASTERS', 18)}}的其他基金
Development of Complex Culture Systems to Study Valvular Dysfunction
开发复杂的培养系统来研究瓣膜功能障碍
- 批准号:
8968385 - 财政年份:2015
- 资助金额:
$ 24.29万 - 项目类别:
Combinatorial analysis of migration stimuli for enhanced wound healing
促进伤口愈合的迁移刺激的组合分析
- 批准号:
8183086 - 财政年份:2011
- 资助金额:
$ 24.29万 - 项目类别:
Combinatorial analysis of migration stimuli for enhanced wound healing
促进伤口愈合的迁移刺激的组合分析
- 批准号:
8469866 - 财政年份:2011
- 资助金额:
$ 24.29万 - 项目类别:
Combinatorial analysis of migration stimuli for enhanced wound healing
促进伤口愈合的迁移刺激的组合分析
- 批准号:
8657060 - 财政年份:2011
- 资助金额:
$ 24.29万 - 项目类别:
Combinatorial analysis of migration stimuli for enhanced wound healing
促进伤口愈合的迁移刺激的组合分析
- 批准号:
8324996 - 财政年份:2011
- 资助金额:
$ 24.29万 - 项目类别:
Creating Engineered Models of Valvular Disease to Study Anti-Calcific Therapies
创建瓣膜疾病工程模型以研究抗钙化疗法
- 批准号:
7797694 - 财政年份:2009
- 资助金额:
$ 24.29万 - 项目类别:
Creating Engineered Models of Valvular Disease to Study Anti-Calcific Therapies
创建瓣膜疾病工程模型以研究抗钙化疗法
- 批准号:
7590174 - 财政年份:2009
- 资助金额:
$ 24.29万 - 项目类别:
Creating Engineered Models of Valvular Disease to Study Anti-Calcific Therapies
创建瓣膜疾病工程模型以研究抗钙化疗法
- 批准号:
8235867 - 财政年份:2009
- 资助金额:
$ 24.29万 - 项目类别:
Creating Engineered Models of Valvular Disease to Study Anti-Calcific Therapies
创建瓣膜疾病工程模型以研究抗钙化疗法
- 批准号:
8055057 - 财政年份:2009
- 资助金额:
$ 24.29万 - 项目类别:
Creating Engineered Models of Valvular Disease to Study Anti-Calcific Therapies
创建瓣膜疾病工程模型以研究抗钙化疗法
- 批准号:
8634811 - 财政年份:2009
- 资助金额:
$ 24.29万 - 项目类别:
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