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Role of gasderminD in ganglion cell dysfunction and injury

Role of gasderminD in ganglion cell dysfunction and injury
GasderminD 在神经节细胞功能障碍和损伤中的作用
批准号:
10326850
负责人:
VALERY I SHESTOPALOV
金额:
$18.61万
依托单位国家:
美国
项目类别:
财政年份:
2021
资助国家:
美国
项目状态:
已结题
起止时间:
2021-02-01 至 2024-01-31

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中文摘要
翻译
在原发性青光眼中,高眼压(OHT)应激触发神经毒性级联反应,导致选择性 视网膜神经节细胞(RGC)死亡。然而,青光眼中机械应激、非缺血应激转化为RGC功能障碍、损伤和死亡的分子机制仍存在较大争议。我们发现 不同强度和持续时间的OHT应激对神经元NLRP1/NLRP3炎性小体的急性激活作用 在体内,IL-1β细胞因子的释放并触发视网膜神经节细胞中GasderminD孔的形成。 这个项目是以我们令人兴奋的初步数据为前提的,其中炎症体阻断抑制了GsdmD 急性和慢性OHT患者视网膜节细胞的激活及预防功能障碍和丢失 (青光眼)模型。我们设计这个项目是为了测试我们的新假设,即代谢和生理 视网膜节细胞功能障碍导致其在OHT损伤中的丢失是通过激活GdmD孔来促进的 线粒体和质膜。如果我们的假设是正确的,那么炎性小体通路的调节 视网膜可以防止青光眼的功能衰退和RGC的丢失。
英文摘要
In primary glaucoma, ocular hypertension (OHT) stress triggers a neurotoxic cascade leading to selective death of retinal ganglion cells (RGC). However, the molecular mechanism transforming mechanical, non-ischemic stress into RGC dysfunction, injury and death in glaucoma remains highly debated. We discovered that OHT stress of various intensity and duration acutely activates neuronal NLRP1/NLRP3 inflammasomes that release of interleukin-1β cytokine and trigger GasderminD pore formation in RGCs in vivo. This project is premised on our exciting preliminary data where inflammasome blockade suppressed GsdmD activation and prevented dysfunction and loss of OHT-challenged RGCs in both acute OHT and chronic OHT (glaucoma) models. We designed this project to test our new hypothesis that metabolic and physiological dysfunction of RGCs leading to their loss in OHT injury is facilitated by activation of GsdmD pores in mitochondria and plasma membranes. If our hypothesis is correct, modulation of inflammasome pathway in the retina would prevent functional decline and loss of RGC in glaucoma.
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会议论文
Diversity and Dynamic Stability of the Ocular Surface Microbiome
  • 批准号:
    8536301
  • 项目类别:
  • 资助金额:
    $63.03万
  • 财政年份:
    2012
  • 负责人:
    VALERY I SHESTOPALOV
  • 依托单位:
The Role of Pannexin1 in Ischemic Injury of Retinal Ganglion Cells
The Role of Pannexin1 in Ischemic Injury of Retinal Ganglion Cells
The Role of Pannexin1 in Ischemic Injury of Retinal Ganglion Cells
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