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:
    10615636
  • 负责人:
  • 金额:
    $ 48.95万
  • 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

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.
项目摘要/摘要 至少有50%接受125i近距离尿治疗的紫菜蛋白酶的患者经历了明显的视力丧失 治疗后3 - 5年内。在正常视网膜中报道了广泛的血管病理学 两年或更长时间后围绕黑色素瘤。这些发现符合被接受的,但并不完整 经过测试的,微血管病会导致辐射相关的视力丧失,原因 辐射过程中的内皮。这导致了几年后的滞后毛细血管损失。如果这个 假设是正确的,可以防止在 视网膜微血管将减少毛细管损失并节省视力。但是,这种方法很难测试 因为尚未确定微血管内皮功能障碍的早期指标。 拟议项目的目标是:促进早期检测,治疗和预防辐射 - 相关的视力丧失。具体来说,我们希望1。检测基于减少的早期内皮功能障碍 血流和对光闪烁2的反应。确定它是否可以预测随后的毛细血管损失和3。 确定辐射引起的内皮功能障碍的分子机制。我们将应用激光斑点 人类的无创,实时成像和测量的流程学(LSFG) 受试者和小鼠检验我们的中心假设,辐射后内皮功能障碍是由 线粒体氧化应激,并可以预测随后的毛细血管辍学的严重程度和 视力丧失。我们将以两个目的检验我们的假设:目标1:确定早期损害是否损害 微血管内皮功能将预测125i后人类的微血管辍学和视力丧失 近距离放射治疗。为此,LSFG,光学相干断层扫描(OCT)和OCT-Angiography(OCT-A) 并将在接受125i近距离治疗的患者中进行视觉功能的测试 用于脉络膜黑色素瘤。我们将测试眼流和闪烁光引起的早期损害 LSFG通过LSFG的血管舒张与随后的视力丧失和毛细血管辍学(如OCT-A检测到)。目的 2:测试选择性抑制在内皮中对身体产生的产生是否可以防止早期减少血液 辐射后的流量和随后的毛细血管损失。在此目标中,遗传鼠标模型在其中关键 线粒体超氧化物产生的调节剂被抑制或过表达,用于测试是否是否 内皮中线粒体ROS的抑制可预防视网膜血流的早期损害, 内皮功能障碍和随后的毛细血管辍学。 拟议的研究的预期结果是对早期辐射视网膜病的生物标志物的了解 以及对内皮细胞线粒体功能障碍在辐射视网膜病变中的作用的见解。我们的研究有 促进与辐射相关视力丧失的一流,有针对性疗法发展的潜力。

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 }}

Isabella Maria Grumbach其他文献

Isabella Maria Grumbach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('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:
    $ 48.95万
  • 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:
    $ 48.95万
  • 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:
    $ 48.95万
  • 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:
    10397594
  • 财政年份:
    2020
  • 资助金额:
    $ 48.95万
  • 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:
    $ 48.95万
  • 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:
    $ 48.95万
  • 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:
    $ 48.95万
  • 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:
    $ 48.95万
  • 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:
    $ 48.95万
  • 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:
    $ 48.95万
  • 项目类别:

相似海外基金

PRECISE (PeRfusion imaging to identify postErior CIrculation candidateS for thrombectomy)
PRECISE(灌注成像以识别血栓切除术的后循环候选者)
  • 批准号:
    10186074
  • 财政年份:
    2021
  • 资助金额:
    $ 48.95万
  • 项目类别:
PRECISE (PeRfusion imaging to identify postErior CIrculation candidateS for thrombectomy)
PRECISE(灌注成像以识别血栓切除术的后循环候选者)
  • 批准号:
    10453667
  • 财政年份:
    2021
  • 资助金额:
    $ 48.95万
  • 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:
    $ 48.95万
  • 项目类别:
Artificial intelligence assisted panoramic Optical Coherence Tomography Angiography for Retinopathy of Prematurity
人工智能辅助全景光学相干断层扫描血管造影治疗早产儿视网膜病变
  • 批准号:
    10612906
  • 财政年份:
    2020
  • 资助金额:
    $ 48.95万
  • 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:
    10397594
  • 财政年份:
    2020
  • 资助金额:
    $ 48.95万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了