Differential susceptibility of αRGCs to glutamate excitotoxicity in autoimmune optic neuritis

自身免疫性视神经炎中αRGC对谷氨酸兴奋性毒性的不同易感性

• 批准号: 280872487
• 负责人: Professor Dr. Andreas Draguhn
• 金额: --
• 依托单位: Abteilung Neuro- und Sinnesphysiologie
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2015
• 资助国家: 德国
• 起止时间: 2014-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/280872487?language=en
• 关键词: Differential; susceptibility; RGCs; glutamate; excitotoxicity

Under autoimmune conditions, elevated neuronal calcium levels may mediate degeneration of both neuronal cell bodies and their axons, acting as a mediator of various insults and injuries involved in inflammatory attack. Identification and blockade of neuronal calcium entry pathways may therefore provide a therapeutic strategy to protect neurons from inflammationassociated death. We will explore these mechanisms in a rat model of autoimmune optic neuritis, where retinal ganglion cells undergo neurodegenerative changes beginning during the early phase of the disease. Our previous experiments have shown that calcium elevation appears to begin in the retina, where retinal ganglion cell bodies reside, before extending to the optic nerves, where their axons are located. Through a combination of in vivo (MRI, evoked potentials) and in vitro (calcium imaging, slice electrophysiology, histopathology) techniques, we will investigate calcium dynamics and calcium channel expression in these cells. Selective blocking experiments will elucidate the contribution that different calcium channels make to neurodegeneration. We will also investigate the potential of targeting these channels to achieve neuroprotection.

在自身免疫条件下，升高的神经元钙水平可能介导神经元胞体及其轴突的退化，作为参与炎症攻击的各种损伤和损伤的媒介。因此，识别和阻断神经元钙离子进入通路可能提供一种保护神经元免受炎症相关死亡的治疗策略。我们将在自身免疫性视神经炎的大鼠模型中探索这些机制，在该模型中，视网膜神经节细胞在疾病的早期就开始经历神经退行性变化。我们以前的实验表明，钙的升高似乎始于视网膜，视网膜神经节细胞体驻留，然后延伸到视神经，它们的轴突位于那里。通过体内(MRI、诱发电位)和体外(钙成像、切片电生理学、组织病理学)技术的结合，我们将研究这些细胞的钙动力学和钙通道表达。选择性阻断实验将阐明不同的钙通道对神经退行性变的贡献。我们还将研究靶向这些通道以实现神经保护的可能性。