Metabolomics a Novel Tool for Investigating the Pathogenesis of Age-related Macular Degeneration

代谢组学是研究年龄相关性黄斑变性发病机制的新工具

基本信息

  • 批准号:
    10361569
  • 负责人:
  • 金额:
    $ 40.76万
  • 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:
    2020-03-01 至 2025-02-28
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly in developed nations, representing a significant socioeconomic burden. Even though its multifactorial nature is well recognized, the pathogenesis of AMD is not fully understood. This has led to the current absence of treatments for dry AMD and lack of reliable ways to determine risk prediction for progression. Thus, there is great need for better understanding of AMD pathobiology and identification of biomarkers. Our group has reported (PMID 28542375, 28916333 and 30672297) and there is new data showing that metabolomics—the qualitative and quantitative analysis of metabolites (molecules <1 kDa)—is an appropriate approach to address these needs. While the metabolome is downstream of the genome, transcriptome, and proteome, it is simultaneously impacted by a wide range of environmental exposures. Therefore, the metabolome closely represents phenotype, as demonstrated in complex conditions, such as cancer and Alzheimer’s disease. To evaluate the role of metabolomics in AMD, we initiated a cross sectional study in which we prospectively recruited 491 patients, obtained an ophthalmological exam and collected fasting blood and urine samples. Analysis of the blood samples identified changes in the metabolomics profile of patients with AMD compared to controls, with differences across AMD severity stages. These differences were mostly found in the lipid pathways, in particular glycerophospholipids and sphingolipids, and purines. In this application, our goal is to provide novel insights into the pathogenesis of AMD, and to identify metabolomic signals that can lead to future biomarkers of this disease and its progression. To do so, we will further characterize the metabolome of AMD. This will be achieved by: 1) performing tissue metabolomics in donor eyes with AMD and control eyes using mass spectrometry (Aim 1A), and assessing correlations between the metabolomic profiles of AMD in tissue and biofluids (i.e. plasma and urine) (Aim 1B); 2) re- assessing our study cohort with early and intermediate AMD, five years after the initial enrolment, with the same protocols, to compare the metabolome of AMD-progressors versus non progressors (Aim 2); and 3) studying the associations between genes linked with AMD risk and metabolomics profiles (Aim 3A), and identifying new metabolite-AMD associations (Aim 3B). This project will provide a unique strategy to increase the current understanding of AMD pathogenesis. By performing tissue metabolomics and studying metabolomics-gene interactions, this proposal will help in identifying new targets for prevention and earlier intervention, thus reducing the burden of AMD. Additionally, this work has the potential to identify biological biomarkers of AMD and disease progression at five years in accessible biofluids, which may contribute to improved screening and risk assessment of AMD and usher in an era of precision medicine for this blinding condition.
项目摘要 视网膜相关性黄斑变性(AMD)是发达国家老年人失明的主要原因。 这是一个巨大的社会经济负担。尽管它的多因素性质 虽然已经认识到,但AMD的发病机制尚未完全了解。这导致目前缺乏治疗方法 干性AMD和缺乏可靠的方法来确定进展的风险预测。因此,非常需要 更好地理解AMD病理生物学和鉴定生物标志物。 我们的小组已经报告(PMID 28542375、28916333和30672297),新数据显示 代谢组学-代谢物(分子<1 kDa)的定性和定量分析-是一种 采取适当的措施来满足这些需求。虽然代谢组位于基因组的下游, 转录组和蛋白质组,它同时受到广泛的环境暴露的影响。 因此,代谢组密切代表表型,如在复杂条件下所证明的,例如 癌症和老年痴呆症。为了评估代谢组学在AMD中的作用,我们启动了一项横断面研究, 在这项研究中,我们前瞻性地招募了491名患者,进行眼科检查,并收集 空腹血样和尿样血液样本的分析确定了代谢组学特征的变化 与对照组相比,AMD患者的AMD严重程度不同。这些差异 主要发现于脂质途径,特别是甘油磷脂和鞘脂以及嘌呤。 在这项申请中,我们的目标是提供新的见解AMD的发病机制,并确定 代谢组学信号可以导致这种疾病及其进展的未来生物标志物。为此,我们将 进一步表征AMD的代谢组。这将通过以下方式实现:1)在组织中进行组织代谢组学研究, 使用质谱法(Aim 1A)对患有AMD的供体眼和对照眼进行分析,并评估相关性 AMD在组织和生物流体(即血浆和尿液)中的代谢组学谱之间的关系(目的1B); 2)重新- 评估我们的研究队列与早期和中期AMD,五年后,首次登记,与 相同的方案,以比较AMD进展者与非进展者的代谢组(目的2);以及3) 研究与AMD风险相关的基因与代谢组学特征之间的关联(Aim 3A),以及 鉴定新的代谢物-AMD关联(目的3B)。 该项目将提供一个独特的策略,以增加目前的AMD发病机制的理解。 通过进行组织代谢组学和研究代谢组学-基因相互作用,这项建议将有助于 确定预防和早期干预的新目标,从而减轻AMD的负担。此外,本发明还 这项工作有可能在5年内确定AMD和疾病进展的生物标志物, 可获得的生物液体,这可能有助于改善AMD的筛查和风险评估,并迎来一个新的治疗方案。 精准医疗时代的到来

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 }}

Deeba Husain其他文献

Deeba Husain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('Deeba Husain', 18)}}的其他基金

Metabolomics a Novel Tool for Investigating the Pathogenesis of Age-related Macular Degeneration
代谢组学是研究年龄相关性黄斑变性发病机制的新工具
  • 批准号:
    10579904
  • 财政年份:
    2020
  • 资助金额:
    $ 40.76万
  • 项目类别:
Metabolomics a Novel Tool for Investigating the Pathogenesis of Age-related Macular Degeneration
代谢组学是研究年龄相关性黄斑变性发病机制的新工具
  • 批准号:
    9885505
  • 财政年份:
    2020
  • 资助金额:
    $ 40.76万
  • 项目类别:

相似海外基金

Hormone therapy, age of menopause, previous parity, and APOE genotype affect cognition in aging humans.
激素治疗、绝经年龄、既往产次和 APOE 基因型会影响老年人的认知。
  • 批准号:
    495182
  • 财政年份:
    2023
  • 资助金额:
    $ 40.76万
  • 项目类别:
Investigating how alternative splicing processes affect cartilage biology from development to old age
研究选择性剪接过程如何影响从发育到老年的软骨生物学
  • 批准号:
    2601817
  • 财政年份:
    2021
  • 资助金额:
    $ 40.76万
  • 项目类别:
    Studentship
RAPID: Coronavirus Risk Communication: How Age and Communication Format Affect Risk Perception and Behaviors
RAPID:冠状病毒风险沟通:年龄和沟通方式如何影响风险认知和行为
  • 批准号:
    2029039
  • 财政年份:
    2020
  • 资助金额:
    $ 40.76万
  • 项目类别:
    Standard Grant
Neighborhood and Parent Variables Affect Low-Income Preschool Age Child Physical Activity
社区和家长变量影响低收入学龄前儿童的身体活动
  • 批准号:
    9888417
  • 财政年份:
    2019
  • 资助金额:
    $ 40.76万
  • 项目类别:
The affect of Age related hearing loss for cognitive function
年龄相关性听力损失对认知功能的影响
  • 批准号:
    17K11318
  • 财政年份:
    2017
  • 资助金额:
    $ 40.76万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Affect regulation and Beta Amyloid: Maturational Factors in Aging and Age-Related Pathology
影响调节和 β 淀粉样蛋白:衰老和年龄相关病理学中的成熟因素
  • 批准号:
    9320090
  • 财政年份:
    2017
  • 资助金额:
    $ 40.76万
  • 项目类别:
Affect regulation and Beta Amyloid: Maturational Factors in Aging and Age-Related Pathology
影响调节和 β 淀粉样蛋白:衰老和年龄相关病理学中的成熟因素
  • 批准号:
    10166936
  • 财政年份:
    2017
  • 资助金额:
    $ 40.76万
  • 项目类别:
Affect regulation and Beta Amyloid: Maturational Factors in Aging and Age-Related Pathology
影响调节和 β 淀粉样蛋白:衰老和年龄相关病理学中的成熟因素
  • 批准号:
    9761593
  • 财政年份:
    2017
  • 资助金额:
    $ 40.76万
  • 项目类别:
How age dependent molecular changes in T follicular helper cells affect their function
滤泡辅助 T 细胞的年龄依赖性分子变化如何影响其功能
  • 批准号:
    BB/M50306X/1
  • 财政年份:
    2014
  • 资助金额:
    $ 40.76万
  • 项目类别:
    Training Grant
Inflamm-aging: What do we know about the effect of inflammation on HIV treatment and disease as we age, and how does this affect our search for a Cure?
炎症衰老:随着年龄的增长,我们对炎症对艾滋病毒治疗和疾病的影响了解多少?这对我们寻找治愈方法有何影响?
  • 批准号:
    288272
  • 财政年份:
    2013
  • 资助金额:
    $ 40.76万
  • 项目类别:
    Miscellaneous Programs
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了