Laser speckle flowgraphy as early indicator of microvasculopathy in radiation-induced vision loss
激光散斑血流成像作为辐射引起的视力丧失中微血管病变的早期指标
基本信息
- 批准号:10397594
- 负责人:
- 金额:$ 47.48万
- 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:2020-05-01 至 2025-04-30
- 项目状态:未结题
- 来源:
- 关键词:AdultAftercareAngiographyAnimal ModelBlindnessBlood VesselsBlood capillariesBlood flowBrachytherapyChoroid MelanomaDataDevelopmentDropoutEarly DiagnosisEndothelial CellsEndotheliumEyeEye diseasesFundingFutureGeneticGoalsHumanImageImpairmentInfusion proceduresInjuryKnowledgeLasersLightLungMalignant NeoplasmsMeasurementMeasuresMediator of activation proteinMethodsMissionMitochondriaModalityMolecularMusNon-Invasive Cancer DetectionOcular MelanomaOptical Coherence TomographyOrganOutcomeOxidative StressPathologyPatientsPerimetryPilot ProjectsPreventionProductionProspective cohortProtocols documentationPublic HealthRadiationReactive Oxygen SpeciesReportingResearchResearch SupportRetinaRetinal DiseasesRoleSeedsSeveritiesStructureSuperoxidesTestingTissuesUnited States National Institutes of HealthUveal MelanomaVasodilationVisionVisual AcuityVisual impairmentbasechoroidal circulationcohortdensityearly detection biomarkersendothelial dysfunctionexperiencegenetic approachhuman datahuman subjectin vivoinsightmelanomamitochondrial dysfunctionmouse modelnovelnovel therapeuticsoverexpressionpreventprogramsprospectiveradiation-induced injuryreal-time imagesresponseretina circulationretinal damagestandard caretargeted treatment
项目摘要
PROJECT SUMMARY/ABSTRACT
At least 50% of patients treated with 125I brachytherapy for uveal melanoma experience significant vision loss
within 3-5 years after therapy. Extensive vascular pathology has been reported in the normal retina
surrounding the melanoma after 2 years or more. These findings are in line with the accepted, but incompletely
tested, concept that microangiopathy causes radiation-related vision loss due to injury of the microvascular
endothelium during radiation. This leads to progressive capillary loss after a lag period of several years. If this
hypothesis is correct, preventing the development of, or treating, radiation-induced endothelial damage in
retinal microvessels will reduce capillary loss and save vision. However, this approach has been difficult to test
because early indicators of microvascular endothelial dysfunction have yet to be established.
The objectives of the proposed project are to: facilitate earlier detection, treatment and prevention of radiation-
associated vision loss. Specifically, we expect to 1. detect early endothelial dysfunction based on reduced
blood flow and response to light flicker 2. determine whether it is predictive of subsequent capillary loss and 3.
identify molecular mechanisms of radiation-induced endothelial dysfunction. We will apply laser speckle
flowgraphy (LSFG) for noninvasive, real-time imaging and measurement of ocular blood flow, in human
subjects and mice to test our central hypothesis, that post-radiation endothelial dysfunction is driven by
mitochondrial oxidative stress, and is predictive of the severity of subsequent capillary dropout and
vision loss. We will test our hypothesis in two aims: Aim 1: Establish whether early impairment of the
microvascular endothelial function will predict microvessel drop-out and vision loss in humans after 125I
brachytherapy. For this purpose, LSFG, optical coherence tomography (OCT) and OCT-angiography (OCT-A)
and tests of visual function will be performed in a prospective cohort of patients undergoing 125I brachytherapy
for choroidal melanoma. We will test whether early impairment of ocular blood flow and flicker light-induced
vasodilation by LSFG correlate with subsequent vision loss and capillary drop-out (as detected by OCT-A). Aim
2: Test whether selective inhibition of mitoROS production in endothelium prevents the early reduction of blood
flow and subsequent loss of capillaries after radiation. In this aim, genetic mouse models in which key
regulators of mitochondrial superoxide production are inhibited or overexpressed will be used to test whether
inhibition of mitochondrial ROS in the endothelium protects from early impairment of retinal blood flow,
endothelial dysfunction and subsequent capillary dropout.
The expected outcomes of the proposed studies are knowledge of biomarkers of early radiation retinopathy
and insights into the role of endothelial-cell mitochondrial dysfunction in radiation retinopathy. Our studies have
the potential to facilitate the development of first-in-class, targeted therapies for radiation-related vision loss.
项目总结/文摘
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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Isabella Maria Grumbach其他文献
Isabella Maria Grumbach的其他文献
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{{ truncateString('Isabella Maria Grumbach', 18)}}的其他基金
Leveraging the mitochondrial regulator MIRO1 to prevent neointimal hyperplasia
利用线粒体调节剂 MIRO1 预防新内膜增生
- 批准号:
10531906 - 财政年份:2021
- 资助金额:
$ 47.48万 - 项目类别:
Leveraging the mitochondrial regulator MIRO1 to prevent neointimal hyperplasia
利用线粒体调节剂 MIRO1 预防新内膜增生
- 批准号:
10384519 - 财政年份:2021
- 资助金额:
$ 47.48万 - 项目类别:
Laser speckle flowgraphy as early indicator of microvasculopathy in radiation-induced vision loss
激光散斑血流成像作为辐射引起的视力丧失中微血管病变的早期指标
- 批准号:
10160909 - 财政年份:2020
- 资助金额:
$ 47.48万 - 项目类别:
Laser speckle flowgraphy as early indicator of microvasculopathy in radiation-induced cognitive decline
激光散斑血流成像作为辐射引起的认知衰退中微血管病变的早期指标
- 批准号:
10282945 - 财政年份:2020
- 资助金额:
$ 47.48万 - 项目类别:
Laser speckle flowgraphy as early indicator of microvasculopathy in radiation-induced vision loss
激光散斑血流成像作为辐射引起的视力丧失中微血管病变的早期指标
- 批准号:
10615636 - 财政年份:2020
- 资助金额:
$ 47.48万 - 项目类别:
CaMKII as a regulator of diabetic retinopathy
CaMKII 作为糖尿病视网膜病变的调节因子
- 批准号:
9468258 - 财政年份:2015
- 资助金额:
$ 47.48万 - 项目类别:
CaMKII as a regulator of diabetic retinopathy
CaMKII 作为糖尿病视网膜病变的调节因子
- 批准号:
8820648 - 财政年份:2015
- 资助金额:
$ 47.48万 - 项目类别:
CaMKII as a regulator of diabetic retinopathy
CaMKII 作为糖尿病视网膜病变的调节因子
- 批准号:
8996072 - 财政年份:2015
- 资助金额:
$ 47.48万 - 项目类别:
CaMKII regulates key mechanisms of vascular response to injury in vivo
CaMKII 调节体内血管损伤反应的关键机制
- 批准号:
8459392 - 财政年份:2012
- 资助金额:
$ 47.48万 - 项目类别:
CaMKII regulates key mechanisms of vascular response to injury in vivo
CaMKII 调节体内血管损伤反应的关键机制
- 批准号:
9029343 - 财政年份:2012
- 资助金额:
$ 47.48万 - 项目类别:
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