Temporal Resolution of Misfolded Prion Protein Transport, Accumulation, Glial Activation, and Neuronal Death in the Retinas of Mice Inoculated with Scrapie
Temporal Resolution of Misfolded Prion Protein Transport, Accumulation, Glial Activation, and Neuronal Death in the Retinas of Mice Inoculated with Scrapie
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DOI：
10.1016/j.ajpath.2016.05.018
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发表时间：
2016-09-01
影响因子：
6
通讯作者：
Greenlee, Justin
中科院分区：
文献类型：
--
作者：
Greenlee, M. Heather West;Lind, Melissa;Greenlee, Justin
目前，缺乏描述体内朊病毒疾病进展的病理标志。我们的目标是使用一个实验模型来确定错误折叠朊蛋白（PrPSc）从大脑到视网膜的运输、PrPSc在视网膜中的积累、周围视网膜组织的反应和神经元损失之间的时间关系。分别在接种后30、60、90、105和120天（dpi）或出现临床疾病症状（153 dpi）时收集接种RML痒病小鼠的视网膜样本。检测视网膜匀浆的朊病毒播种活性。抗体染色用于评估PrPSc的积累和视网膜组织的反应。光感受器的丧失被用来衡量神经元的死亡。所有样品在60 dpi时首次检测到PrPSc的播种活性。在90 dpi处首次检测到PrPSc的积累和视网膜胶质细胞的同步激活。在105dpi处首次检测到小胶质细胞的激活，但直到120dpi才检测到神经元死亡。我们的结果表明，通过使用视网膜，我们可以解决朊病毒疾病发病过程中几个关键事件之间的时间分离。
Currently, there is a lack of pathological landmarks to describe the progression of prion disease in vivo. Our goal was to use an experimental model to determine the temporal relationship between the transport of misfolded prion protein (PrPSc) from the brain to the retina, the accumulation of PrPSc in the retina, the response of the surrounding retinal tissue, and loss of neurons. Retinal samples from mice inoculated with RML scrapie were collected at 30, 60, 90, 105, and 120 days post inoculation (dpi) or at the onset of clinical signs of disease (153 dpi). Retinal homogenates were tested for prion seeding activity. Antibody staining was used to assess accumulation of PrPSc and the resulting response of retinal tissue. Loss of photoreceptors was used as a measure of neuronal death. PrPSc seeding activity was first detected in all samples at 60 dpi. Accumulation of PrPSc and coincident activation of retinal glia were first detected at 90 dpi. Activation of microglia was first detected at 105 dpi, but neuronal death was not detectable until 120 dpi. Our results demonstrate that by using the retina we can resolve the temporal separation between several key events in the pathogenesis of prion disease.