RPE Exosomes in Age-related Macular Degeneration
RPE Exosomes in Age-related Macular Degeneration
批准号:
10541821
负责人:
Belinda J Hernandez
金额:
$3.95万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2022
资助国家:
美国
项目状态:
未结题
起止时间:
2022-01-01 至 2025-05-14
关键词:
AddressAgeAge related macular degenerationAgingAmericanApicalAreaBehaviorBiologicalBiological Response Modifier TherapyBiologyBlindnessBloodBlood-Retinal BarrierBruch&aposs basal membrane structureCell Culture TechniquesCharacteristicsCholesterolChoroidCirculationClinicalCollagenComplementComplement Factor HComplexDepositionDetectionDeveloped CountriesDevelopmentDietDiseaseDisease ProgressionDrusenEarly DiagnosisEconomic BurdenElastinElderlyEndosomesExperimental DesignsExposure toExtracellular MatrixEyeEye diseasesFamily suidaeFatty acid glycerol estersFrequenciesFunctional disorderGeneticGenetic RiskGoalsHealthIn VitroInflammationInterventionLabelLinkLipidsLipoproteinsMaintenanceMicroRNAsModelingMolecularMusNational Eye InstituteNational Institute on AgingNatural regenerationOnset of illnessOxidative StressPathologicPathologyPathway interactionsPatientsPhotoreceptorsPlasmaProcessProtein SecretionProteinsQuality of lifeRetinaRetinal DegenerationRetinal DiseasesRetinal PigmentsRisk FactorsRoleSideStressStructure of retinal pigment epitheliumTestingTherapeuticTherapeutic InterventionUrineVisionenvironmental stressorexosomeextracellular vesiclesgene therapygenetic approachhealthy agingimprovedin vivoinsightmonolayermouse modelnanovesiclenovelnovel virusoxidized lipidparticlepharmacologicresponserisk variantsocioeconomicssolutestressor
中文摘要
摘要
英文摘要
Abstract
Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in the elderly in
developed countries, and there are limited therapeutic options. The earliest clinical signs are lipid and protein
deposits known as drusen, that form between the retinal pigmented epithelium (RPE) and the adjacent
pentalaminar collagenous extracellular matrix, Bruch’s membrane. The RPE functions to maintain the outer
blood-retinal barrier and to support photoreceptor function, including regeneration of visual pigment and
turnover of outer segments. Dysfunction of the RPE underlies pathology leading to AMD. It is thought that in
AMD this dysregulation in RPE cells is at least in part responsible for the formation of drusen. At present, the
exact mechanisms for drusen formation are unknown. A potential approach to detect early AMD patho-
biological changes is through the isolation of exosomes, which are nanovesicles that can be purified from
biofluids (e.g. plasma and urine). Since RPE-released exosomes and other extracellular vesicles are essential
parts of the endosomal pathway, I hypothesize that exosomes released from stressed RPE cells are
distinct from those released from unstressed RPE cells, and that these exosomes are involved in the
pathognomonic deposit formation and ECM changes that underlie the early and late stages of AMD. By
evaluating two complementary in vitro and in vivo AMD models, our goal for this project is to determine the role
of exosome secretion in sub-RPE deposit formation and in ECM changes under conditions relevant to AMD,
and whether pharmacological or gene therapy/biological therapeutic interventions are possible. In the first
aim, I will characterize and quantify the protein and lipid composition of sub-RPE deposits, ECM and basal-
side exosomes in RPE stressed by pathophysiological conditions implicated in AMD (oxidative stress,
complement dysregulation, and age), while modulating exosome release by both pharmacological and genetic
approaches. In the second aim, I will molecularly tag, isolate and characterize RPE-derived exosomes from
the blood of a well characterized mouse model of early-stage AMD. Detailed profiling of RPE-derived
exosomes in normal and diseased settings represent novel studies that will provide insight into mechanisms
that underlie pathobiological changes in AMD.
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RPE Exosomes in Age-related Macular Degeneration
-
批准号:10311656
-
项目类别:
-
资助金额:$3.79万
-
财政年份:2022
-
负责人:Belinda J Hernandez
-
依托单位:
国内基金
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