Investigating the role of retinal astrocytes in exercise-induced retinal neuroprotection

研究视网膜星形胶质细胞在运动引起的视网膜神经保护中的作用

基本信息

  • 批准号:
    10484539
  • 负责人:
  • 金额:
    --
  • 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
  • 起止时间:
    2022-07-01 至 2027-06-30
  • 项目状态:
    未结题

项目摘要

Photoreceptor dysfunction is one of the hallmark pathologies associated with retinal degenerative (RD) diseases that manifests in patients as a progressive loss of vision. This encompasses heterogenous diseases such as retinitis pigmentosa, which affects 1 in 3500 people worldwide and age-related macular degeneration, which affects over 196 million people worldwide and is projected to reach 288 million people by 2040. Specifically, in our Veteran population, roughly 7,000 Veterans become visually impaired each year due to RD. Clinical trials and retrospective studies suggest that RD patients may respond to exercise as a neuroprotective treatment to preserve vision. Recently, our labs filled a significant knowledge gap by demonstrating that modest exercise protects retinal function and structure in models of RD and were accompanied by increased levels of brain derived neurotrophic factor (BDNF) and required intact BDNF-TrkB signal transduction. To date, the cell-types and molecular processes mediating the neuroprotective benefits of exercise are unknown. Others have shown that astrocytes and endothelial cells in the brain express BDNF and its high-affinity receptor, TrkB, and that altered BDNF-TrkB signaling in these cell-types contributes to neurodegenerative disease progression and severity. Recently, it has been demonstrated that astrocytes modify their morphology in response to BDNF in the brain during neurodegeneration. Likewise, vascular endothelial cells express BDNF under exercise-induced physiological stress. These data suggest that astrocytes and endothelial cells may mediate the neuroprotective effects of exercise in the retina. Our approach is to understand the morphological, gene expression and functional alterations in retinal astrocytes and vasculature induced from exercise and how these alterations contribute to neuroprotection. For this proposal, we will use the BALB/c light induced retinal degeneration model, which exhibits phenotypes found in patients with RD. We hypothesize that exercise induces retinal astrocyte plasticity and improved vascular function through increased BDNF signaling mechanisms, promoting neural repair and protection. In Specific Aim 1, we will investigate if exercise influences retinal astrocyte biology, by assessing retinal astrocyte morphology, cellular gene expression profiles, and retinal astrocyte-mediated phagocytosis. Immunohistochemical labeling, AnalyzeSkeleton and Sholl analysis will be used to quantify astrocyte cell morphology and density. Retinal astrocytes will be isolated using magnetic-activated cell sorting (MACS) to examine astrocyte gene expression profiles. To monitor retinal astrocyte function, a novel in vitro live-imaging of astrocyte-mediated phagocytosis will be used. In Specific Aim 2, we will determine the effects of exercise on retinal vascular morphology, gene expression and function. Angiotool will be used for retinal vascular morphology quantification analysis. Retinal vascular cell gene expression profiles will be assessed by MACS and vascular function will be assessed using retinal functional hyperemia. In Specific Aim 3, we will determine if exercise-induced BDNF signaling mechanisms influence retinal astrocyte and vascular morphology, gene expression and function, by blocking BDNF signaling using a highly specific TrkB receptor antagonist, ANA-12. Retinal astrocyte and vascular assessments performed in Specific Aims 1 and 2 found to be most informative will be used to compare experimental groups. The expected outcome of this study is that exercise-induced BDNF signaling alters retinal astrocyte and vascular morphology, gene expression and improves function in order to promote retinal neuroprotection. Results from this study will illuminate the morphological, gene expression and functional alterations that ultimately result in gain of function(s) and or loss/upregulation of homeostatic function(s) in retinal astrocytes and vasculature. This proposal holds profound potential for the long-term goals of optimizing exercise-based therapeutics and creating new pharmacological strategies targeting the underlying mechanisms of exercise-induced protection in patients with RD that can be extended to other neurodegenerative and neuroinflammatory diseases.
光感受器功能障碍是视网膜变性(RD)相关的标志性病理之一。

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 }}

Katie Leigh Bales其他文献

Katie Leigh Bales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 }}

相似海外基金

Construction of affinity sensors using high-speed oscillation of nanomaterials
利用纳米材料高速振荡构建亲和传感器
  • 批准号:
    23H01982
  • 财政年份:
    2023
  • 资助金额:
    --
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Affinity evaluation for development of polymer nanocomposites with high thermal conductivity and interfacial molecular design
高导热率聚合物纳米复合材料开发和界面分子设计的亲和力评估
  • 批准号:
    23KJ0116
  • 财政年份:
    2023
  • 资助金额:
    --
  • 项目类别:
    Grant-in-Aid for JSPS Fellows
Development of High-Affinity and Selective Ligands as a Pharmacological Tool for the Dopamine D4 Receptor (D4R) Subtype Variants
开发高亲和力和选择性配体作为多巴胺 D4 受体 (D4R) 亚型变体的药理学工具
  • 批准号:
    10682794
  • 财政年份:
    2023
  • 资助金额:
    --
  • 项目类别:
Platform for the High Throughput Generation and Validation of Affinity Reagents
用于高通量生成和亲和试剂验证的平台
  • 批准号:
    10598276
  • 财政年份:
    2023
  • 资助金额:
    --
  • 项目类别:
Collaborative Research: DESIGN: Co-creation of affinity groups to facilitate diverse & inclusive ornithological societies
合作研究:设计:共同创建亲和团体以促进多元化
  • 批准号:
    2233343
  • 财政年份:
    2023
  • 资助金额:
    --
  • 项目类别:
    Standard Grant
Collaborative Research: DESIGN: Co-creation of affinity groups to facilitate diverse & inclusive ornithological societies
合作研究:设计:共同创建亲和团体以促进多元化
  • 批准号:
    2233342
  • 财政年份:
    2023
  • 资助金额:
    --
  • 项目类别:
    Standard Grant
Molecular mechanisms underlying high-affinity and isotype switched antibody responses
高亲和力和同种型转换抗体反应的分子机制
  • 批准号:
    479363
  • 财政年份:
    2023
  • 资助金额:
    --
  • 项目类别:
    Operating Grants
Deconstructed T cell antigen recognition: Separation of affinity from bond lifetime
解构 T 细胞抗原识别:亲和力与键寿命的分离
  • 批准号:
    10681989
  • 财政年份:
    2023
  • 资助金额:
    --
  • 项目类别:
CAREER: Engineered Affinity-Based Biomaterials for Harnessing the Stem Cell Secretome
职业:基于亲和力的工程生物材料用于利用干细胞分泌组
  • 批准号:
    2237240
  • 财政年份:
    2023
  • 资助金额:
    --
  • 项目类别:
    Continuing Grant
ADVANCE Partnership: Leveraging Intersectionality and Engineering Affinity groups in Industrial Engineering and Operations Research (LINEAGE)
ADVANCE 合作伙伴关系:利用工业工程和运筹学 (LINEAGE) 领域的交叉性和工程亲和力团体
  • 批准号:
    2305592
  • 财政年份:
    2023
  • 资助金额:
    --
  • 项目类别:
    Continuing Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了