Microglial Inhibition as a Therapeutic Strategy for Subretinal Hemorrhage

小胶质细胞抑制作为视网膜下出血的治疗策略

基本信息

  • 批准号:
    9555696
  • 负责人:
  • 金额:
    $ 30.45万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
  • 资助国家:
    美国
  • 起止时间:
  • 项目状态:
    未结题

项目摘要

We are continuing working on a mouse model of subretinal hemorrhage that we have created to characterize the inflammatory responses and photoreceptor degeneration that occur in the acute aftermath of hemorrhage. It was observed that microglial infiltration into the outer retina commences as early as 6 hours after hemorrhage. Inflammatory cells progressively accumulate in the outer nuclear layer concurrently with photoreceptor degeneration and apoptosis. Administration of minocycline, an inhibitor of microglial activation, decreased microglial expression of chemotactic cytokines in vitro and reduced microglial infiltration and photoreceptor cell loss after subretinal hemorrhage in vivo. Currently, we are employing this model to examine microglial communications with Muller cells, particularly that underlying TSPO-mediated signaling. We found that microglial activation in this model is accompanied by the induced expression of TSPO. The inducibility and effects of TSPO signaling in the retina reveal a mechanism of coordinated macroglia-microglia interactions, the function of which is to limit the magnitude of inflammatory responses after their initiation, facilitating a return to baseline quiescence. Our results indicate that TSPO is a promising molecular marker for imaging inflammatory cell activation in the retina and highlight DBI-TSPO signaling as a potential target for immodulatory therapies.
我们正在继续研究视网膜下出血的小鼠模型,我们已经建立了这个模型来表征出血后急性发作时的炎症反应和感光细胞退化。观察到小胶质细胞早在出血后6h就开始渗入视网膜外。伴随着感光细胞变性和细胞凋亡,炎性细胞逐渐聚集在外核层。小胶质细胞激活抑制剂米诺环素在体外可减少小胶质细胞趋化因子的表达,减少视网膜下出血后小胶质细胞的浸润和光感受器细胞的丢失。 目前,我们正在使用这个模型来研究小胶质细胞与Muller细胞的通讯,特别是TSPO介导的信号传导。我们发现,在这个模型中,小胶质细胞的激活伴随着TSPO的诱导表达。TSPO信号在视网膜中的诱导和作用揭示了大胶质细胞和小胶质细胞协调相互作用的机制,其功能是在启动炎症反应后限制其大小,促进恢复到基线的静止。我们的结果表明,TSPO是一种很有前途的分子标志物,可以用来成像视网膜中的炎性细胞激活,并强调DBI-TSPO信号是一种潜在的非调节性治疗的靶点。

项目成果

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Wai Wong其他文献

Wai Wong的其他文献

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{{ truncateString('Wai Wong', 18)}}的其他基金

Dynamic Imaging of Retinal Microglia
视网膜小胶质细胞的动态成像
  • 批准号:
    7968406
  • 财政年份:
  • 资助金额:
    $ 30.45万
  • 项目类别:
The Age-Related Eye Disease Study 2 (AREDS2)
年龄相关眼病研究 2 (AREDS2)
  • 批准号:
    8339797
  • 财政年份:
  • 资助金额:
    $ 30.45万
  • 项目类别:
Dynamic Imaging of Retinal Microglia
视网膜小胶质细胞的动态成像
  • 批准号:
    8938327
  • 财政年份:
  • 资助金额:
    $ 30.45万
  • 项目类别:
Dynamic Imaging of Retinal Microglia
视网膜小胶质细胞的动态成像
  • 批准号:
    7734660
  • 财政年份:
  • 资助金额:
    $ 30.45万
  • 项目类别:
The Age-Related Eye Disease Study 2 (AREDS2)
年龄相关眼病研究 2 (AREDS2)
  • 批准号:
    8149206
  • 财政年份:
  • 资助金额:
    $ 30.45万
  • 项目类别:
Dynamic Imaging of Retinal Microglia
视网膜小胶质细胞的动态成像
  • 批准号:
    8149190
  • 财政年份:
  • 资助金额:
    $ 30.45万
  • 项目类别:
The Age-Related Eye Disease Study 2 (AREDS2)
年龄相关眼病研究 2 (AREDS2)
  • 批准号:
    7968435
  • 财政年份:
  • 资助金额:
    $ 30.45万
  • 项目类别:
AMD Phenotype and Genotype Study
AMD 表型和基因型研究
  • 批准号:
    8737693
  • 财政年份:
  • 资助金额:
    $ 30.45万
  • 项目类别:
Role of Microglia in the Retina in Retinal Diseases
视网膜小胶质细胞在视网膜疾病中的作用
  • 批准号:
    10266906
  • 财政年份:
  • 资助金额:
    $ 30.45万
  • 项目类别:
Role of Microglia in the Retina in Retinal Diseases
视网膜小胶质细胞在视网膜疾病中的作用
  • 批准号:
    10020024
  • 财政年份:
  • 资助金额:
    $ 30.45万
  • 项目类别:

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