Elevated Intraocular Pressure Induces Amyloid-β Deposition and Tauopathy in the Lateral Geniculate Nucleus in a Monkey Model of Glaucoma
Elevated Intraocular Pressure Induces Amyloid-β Deposition and Tauopathy in the Lateral Geniculate Nucleus in a Monkey Model of Glaucoma
复制标题
在青光眼猴模型中，眼压升高可诱导外侧膝状核中的淀粉样蛋白沉积和 tau 蛋白病变
DOI：
10.1167/iovs.17-22312
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发表时间：
2017-10-01
影响因子：
4.4
通讯作者：
Zhuo, Yehong
中科院分区：
文献类型：
--
作者：
Yan, Zhichao;Liao, Huanquan;Zhuo, Yehong
目的.最近的证据表明阿尔茨海默病（AD）和青光眼之间存在潜在的关联，并且发现淀粉样蛋白-β（A β）和Tau蛋白在青光眼患者的视网膜中显著沉积。然而，没有一致的发现已经出现关于AD样的变化，在中央视觉系统（CVS）。研究证实A β和Tau神经病理学的存在是必要的，以确定潜在的机制，有助于在青光眼中观察到的视觉障碍。建立恒河猴慢性青光眼模型。对视网膜、视神经、包括外侧膝状体核（LGN）和初级视皮层（VI）在内的CVS以及包括海马（Hpp）在内的认知区域进行了评价。使用免疫组织化学、蛋白质印迹和ELISA在上述结构中测试β 1-42和磷酸化-Tau（p-Tau），并且使用银染色和透射电子显微镜（TEM）观察神经炎斑和嗜银结构/神经丝。免疫组化显示LGN中A β和p-Tau标记阳性。Western blotting和ELISA结果显示，LGN中存在A β和p-Tau蛋白。在初级视觉皮层中也有微弱的β表达。相比之下，海马，这是最严重的影响区域在AD，没有显示出阳性标记。结构上，银染色和透射电镜显示LGN内神经炎性斑块和嗜银结构/神经纤维缠结。据我们所知，这些数据首次共同确立了在昏迷性LGN中存在标志性AD样病理。我们的研究结果可能为开发研究治疗提供新的靶点，从而增强青光眼患者的神经保护作用。
PURPOSE. Recent evidence has suggested a potential association between Alzheimer's disease (AD) and glaucoma and found significant deposition of amyloid-beta (A beta) and Tau protein in the retinas of glaucoma patients. However, no coherent finding has emerged regarding the AD-like changes in the central visual system (CVS). Studies confirming the presence of A beta and Tau neuropathology are warranted to identify the underlying mechanism that contributes to the visual impairment observed in glaucoma.METHODS. A chronic glaucoma model was established in rhesus monkeys. The retina, optic nerve, CVS including the lateral geniculate nucleus (LGN) and primary visual cortex (VI), and cognitive areas including the hippocampus (Hpp) were evaluated. A beta 1-42 and phosphorylated-Tau (p-Tau) were tested in the aforementioned structure using immunohistochemistry, Western blotting and ELISA, and the neuritic plaques and argyrophilic structures/neurofilaments were observed using silver staining and transmission electron microscopy (TEM).RESULTS. Immunohistochemistry revealed positive A beta and p-Tau labeling in the LGN. According to Western blotting assay and ELISA, A beta and p-Tau were present in the LGN. A beta also was expressed weakly in the primary visual cortex. In contrast, the hippocampus, which is the most severely affected region in AD, showed no positive labeling. Structurally, silver staining and TEM revealed neuritic plaques and argyrophilic structures/neurofibrillary tangles, in the LGN.CONCLUSIONS. For the first time to our knowledge, these data collectively establish the existence of hallmark AD-like pathologies in the glaucomatous LGN. Our results may provide new targets for developing research therapies that will enhance neuroprotection in glaucoma patients.