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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Targeting amyloid-β in glaucoma treatment
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Targeting amyloid-β in glaucoma treatment

机译：靶向β淀粉样蛋白治疗青光眼

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摘要

The development of the devastating neurodegenerative condition, Alzheimer's disease, is strongly associated with amyloid-β (Aβ) deposition, neuronal apoptosis, and cell loss. Here, we provide evidence that implicates these same mechanisms in the retinal disease glaucoma, a major cause of irreversible blindness worldwide, previously associated simply with the effects of intraocular pressure. We show that Aβ colocalizes with apoptotic retinal ganglion cells (RGC) in experimental glaucoma and induces significant RGC apoptosis in vivo in a dose- and time-dependent manner. We demonstrate that targeting different components of the Aβ formation and aggregation pathway can effectively reduce glau-comatous RGC apoptosis in vivo, and finally, that combining treatments (triple therapy) is more effective than monotherapy. Our work suggests that targeting the Aβ pathway provides a therapeutic avenue in glaucoma management. Furthermore, our work demonstrates that the combination of agents affecting multiple stages in the Aβ pathway may be the most effective strategy in Aβ-related diseases.
机译：破坏性神经退行性疾病阿尔茨海默氏病的发展与淀粉样β（Aβ）沉积，神经元凋亡和细胞丢失密切相关。在这里，我们提供的证据表明，在视网膜疾病青光眼中涉及这些相同的机制，而青光眼是全世界不可逆性失明的主要原因，以前与眼内压的影响有关。我们显示，Aβ在实验性青光眼中与凋亡性视网膜神经节细胞（RGC）共定位，并在体内以剂量和时间依赖性方式诱导显着的RGC细胞凋亡。我们证明靶向Aβ形成和聚集途径的不同成分可以有效减少体内青光眼样RGC细胞凋亡，最后，联合治疗（三联疗法）比单一疗法更有效。我们的工作表明，靶向Aβ途径可为青光眼的治疗提供治疗途径。此外，我们的工作表明，影响Aβ途径多个阶段的药物组合可能是Aβ相关疾病中最有效的策略。

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