School of Optometry and Vision Sciences, Cardiff University, Cardiff, CF24 4HQ, UK.
UK Dementia Research Institute, Cardiff University, Cardiff, UK.
Acta Neuropathol Commun. 2020 Dec 7;8(1):216. doi: 10.1186/s40478-020-01094-2.
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 APP. 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.
神经元树突和突触修剪是神经退行性疾病的早期特征，包括阿尔茨海默病。除了大脑病理学外，淀粉样斑块沉积、小胶质细胞激活和细胞丢失也发生在人类患者和阿尔茨海默病动物模型的视网膜中。视网膜神经节细胞是视网膜的输出神经元，易受神经退行性疾病的损伤，是进行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，视网膜在阿尔茨海默病模型中的受累程度以及它在多大程度上反映了大脑病理学尚不清楚。在这里，我们对三种研究充分的阿尔茨海默病小鼠模型（Tg2576、3xTg-AD 和 APP）中的视网膜神经节细胞树突结构和海马树突棘进行了定量分析。视网膜外植体中 DiO 标记的视网膜神经节细胞的树突复杂性在所有三种模型中均以年龄、性别和感受野依赖的方式降低。所有三种阿尔茨海默病模型的 DiO 标记海马切片均显示 CA1 树突棘丢失，反映了视网膜中所见的神经退行性病变的早期阶段。形态学分类表明，所有模型中均以薄棘的丢失为主。视网膜神经节细胞树突场减少与所有三种阿尔茨海默病模型中海马树突棘丢失平行发生的事实为使用视网膜神经退行性变提供了有力支持。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，我们的研究提出了一种将视网膜成像作为诊断疾病和监测阿尔茨海默病进展的非侵入性方法。
