Retinal ganglion cell degeneration correlates with hippocampal spine loss in experimental Alzheimer's disease.
Retinal ganglion cell degeneration correlates with hippocampal spine loss in experimental Alzheimer's disease.
复制标题
DOI：
10.1186/s40478-020-01094-2
复制
发表时间：
2020-12-07
影响因子：
7.1
通讯作者：
Morgan JE
中科院分区：
文献类型：
--
作者：
Bevan RJ;Hughes TR;Williams PA;Good MA;Morgan BP;Morgan JE
神经元树突和突触修剪是神经退行性疾病（包括阿尔茨海默病）的早期特征。除了大脑病理学之外，阿尔茨海默病患者和动物模型的视网膜中还存在淀粉样蛋白斑沉积、小胶质细胞激活和细胞丢失。视网膜神经节细胞是视网膜的输出神经元，很容易受到神经退行性疾病的损害，并且是非侵入性临床诊断和监测阿尔茨海默病进展的潜在机会。然而，阿尔茨海默氏症模型中视网膜受累的程度以及这在多大程度上反映了大脑病理学尚不清楚。在这里，我们量化了三种经过充分研究的阿尔茨海默病小鼠模型（Tg2576、3xTg-AD 和 APPNL-G-F）中视网膜神经节细胞树突结构和海马树突棘的变化。在所有三个模型中，来自视网膜外植体的 DiOlistically 标记的视网膜神经节细胞的树突复杂性均以年龄、性别和感受野依赖性方式降低。 DiOlistically 标记的海马切片显示，在所有三种阿尔茨海默氏症模型中，CA1 顶端树突的脊柱缺失，反映了视网膜中神经退行性变的早期阶段。形态学分类显示，细刺的损失占主导地位。在所有三种阿尔茨海默病模型中，视网膜神经节细胞树突状区域减少与海马树突棘损失同时发生，这为视网膜神经变性的使用提供了令人信服的支持。由于视网膜树突变化处于当前临床成像系统（例如光学相干断层扫描）的光学范围内，因此我们的研究证明将视网膜成像作为一种非侵入性方法来诊断疾病和监测阿尔茨海默病的进展。
Neuronal dendritic and synaptic pruning are early features of neurodegenerative diseases, including Alzheimer’s disease. In addition to brain pathology, amyloid plaque deposition, microglial activation, and cell loss occur in the retinas of human patients and animal models of Alzheimer’s disease. Retinal ganglion cells, the output neurons of the retina, are vulnerable to damage in neurodegenerative diseases and are a potential opportunity for non-invasive clinical diagnosis and monitoring of Alzheimer’s progression. However, the extent of retinal involvement in Alzheimer’s models and how well this reflects brain pathology is unclear. Here we have quantified changes in retinal ganglion cells dendritic structure and hippocampal dendritic spines in three well-studied Alzheimer’s mouse models, Tg2576, 3xTg-AD and APPNL-G-F. Dendritic complexity of DiOlistically labelled retinal ganglion cells from retinal explants was reduced in all three models in an age-, gender-, and receptive field-dependent manner. DiOlistically labelled hippocampal slices showed spine loss in CA1 apical dendrites in all three Alzheimer’s models, mirroring the early stages of neurodegeneration as seen in the retina. Morphological classification showed that loss of thin spines predominated in all. The demonstration that retinal ganglion cells dendritic field reduction occurs in parallel with hippocampal dendritic spine loss in all three Alzheimer’s models provide compelling support for the use of retinal neurodegeneration. As retinal dendritic changes are within the optical range of current clinical imaging systems (for example optical coherence tomography), our study makes a case for imaging the retina as a non-invasive way to diagnose disease and monitor progression in Alzheimer’s disease.
登录
查看更多内容
影响因子：
5.7
作者：
Koronyo-Hamaoui, Maya;Koronyo, Yosef;Ljubimov, Alexander V.;Miller, Carol A.;Ko, MinHee K.;Black, Keith L.;Schwartz, Michal;Farkas, Daniel L.
通讯作者：
Farkas, Daniel L.
影响因子：
16.2
作者：
Berry KP;Nedivi E
通讯作者：
Nedivi E
影响因子：
9
作者：
Grimaldi A;Brighi C;Peruzzi G;Ragozzino D;Bonanni V;Limatola C;Ruocco G;Di Angelantonio S
通讯作者：
Di Angelantonio S
影响因子：
7.8
作者：
Belfiore, Ramona;Rodin, Alexis;Oddo, Salvatore
通讯作者：
Oddo, Salvatore
DOI：
10.1016/j.dadm.2018.10.006
发表时间：
2019-12-01
影响因子：
5.3
作者：
Liu, Yao-Lin;Hsieh, Yi-Ting;Chen, Yen-Ching
通讯作者：
Chen, Yen-Ching