Abstract：
Neurofibrillary tangles (NFT), a neuronal lesion found in Alzheimer\'s disease (AD), are composed of fibrillary aggregates of modified forms of tau proteins. The propagation of NFT follows neuroanatomical pathways suggesting that synaptically connected neurons could transmit tau pathology by the recruitment of normal tau in a prion-like manner. Moreover, the intracerebral injection of pathological tau from AD brains induces the seeding of normal tau in mouse brain. Creutzfeldt-Jacob disease has been transmitted after ocular transplants of cornea or sclera and the scrapie agent can spread across the retino-tectal pathway after intraocular injection of scrapie mouse brain homogenates. In AD, a tau pathology has been detected in the retina. To investigate the potential risk of tau pathology transmission during eye surgery using AD tissue material, we have analysed the development of tau pathology in the visual pathway of mice models expressing murine tau, wild-type or mutant human tau after intraocular injection of pathological tau proteins from AD brains. Although these pathological tau proteins were internalized in retinal ganglion cells, they did not induce aggregation of endogenous tau nor propagation of a tau pathology in the retino-tectal pathway after a 6-month incubation period. These results suggest that retinal ganglion cells exhibit a resistance to develop a tau pathology, and that eye surgery is not a major iatrogenic risk of transmission of tau pathology, contrary to what has been observed for transmission of infectious prions in prion diseases.
摘要：
神经原纤维缠结(NFT),在阿尔茨海默病（AD）中发现的神经元病变，由修饰形式的tau蛋白的原纤维聚集体组成。NFT的传播遵循神经解剖学途径，表明突触连接的神经元可以通过以朊病毒样方式募集正常tau来传播tau病理。此外，脑内注射AD脑中的病理性tau诱导小鼠脑中正常tau的接种。Creutzfeldt-Jacob病已在角膜或巩膜的眼部移植后传播，并且在眼内注射瘙痒病小鼠脑匀浆后，瘙痒病剂可在视网膜-顶盖途径中传播。在AD中,在视网膜中检测到tau病理。为了调查使用AD组织材料在眼科手术期间tau病理学传播的潜在风险，我们已经分析了Tau病理学在表达小鼠模型的视觉通路中的发展，眼内注射AD脑中病理性tau蛋白后，野生型或突变型人tau。尽管这些病理性tau蛋白在视网膜神经节细胞中被内化，在6个月的潜伏期后，它们不会在retino-tectal途径中诱导内源性tau的聚集或tau病理的传播。这些结果表明，视网膜神经节细胞表现出对形成tau病理学的抵抗力，眼科手术并不是导致tau病理学传播的主要医源性风险，与在朊病毒疾病中观察到的传染性朊病毒的传播相反。
