An ocular glymphatic clearance system removes β-amyloid from the rodent eye
An ocular glymphatic clearance system removes β-amyloid from the rodent eye
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DOI：
10.1126/scitranslmed.aaw3210
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发表时间：
2020-03-25
影响因子：
17.1
通讯作者：
Nedergaard, Maiken
中科院分区：
文献类型：
--
作者：
Wang, Xiaowei;Lou, Nanhong;Nedergaard, Maiken
尽管高代谢活动，视网膜和视神经乳头缺乏传统的淋巴引流。我们在此确定了啮齿动物通过近端视神经清除液体和废物的眼部胶质淋巴途径。β-淀粉样蛋白（A β）通过依赖于神经胶质水通道水通道蛋白-4（AQP 4）的途径从视网膜和玻璃体中清除，并由眼-颅压差驱动。穿过椎板屏障后，轴突内A β通过静脉周围间隙被清除，随后被引流到淋巴管。光诱导的瞳孔收缩增强流出，而阿托品或颅内压升高阻断流出。在两种不同的小鼠青光眼模型中，A.通过板层屏障的缺陷而不是定向轴突流出而从眼睛泄漏。结果表明，在啮齿类动物中，从眼内空间中清除液体和代谢物是通过胶质淋巴途径发生的，这可能在青光眼中受损。
Despite high metabolic activity, the retina and optic nerve head lack traditional lymphatic drainage. We here identified an ocular glymphatic clearance route for fluid and wastes via the proximal optic nerve in rodents. beta-amyloid (A beta) was cleared from the retina and vitreous via a pathway dependent on glial water channel aquaporin-4 (AQP4) and driven by the ocular-cranial pressure difference. After traversing the lamina barrier, intra-axonal A beta was cleared via the perivenous space and subsequently drained to lymphatic vessels. Light-induced pupil constriction enhanced efflux, whereas atropine or raising intracranial pressure blocked efflux. In two distinct murine models of glaucoma, A. leaked from the eye via defects in the lamina barrier instead of directional axonal efflux. The results suggest that, in rodents, the removal of fluid and metabolites from the intraocular space occurs through a glymphatic pathway that might be impaired in glaucoma.