An ocular glymphatic clearance system removes β-amyloid from the rodent eye

• Published in: Science translational medicine 2020-03, Vol.12 (536)
• Main Authors: Wang, Xiaowei, Lou, Nanhong, Eberhardt, Allison, Yang, Yujia, Kusk, Peter, Xu, Qiwu, Förstera, Benjamin, Peng, Sisi, Shi, Meng, Ladrón-de-Guevara, Antonio, Delle, Christine, Sigurdsson, Björn, Xavier, Anna L R, Ertürk, Ali, Libby, Richard T, Chen, Lu, Thrane, Alexander S, Nedergaard, Maiken
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Amyloid beta-Peptides - metabolism; Animal models; Animals; Aquaporin 4; Aquaporin 4 - metabolism; Atropine; Glaucoma; Glymphatic System - metabolism; Intracranial Pressure; Light effects; Lymphatic drainage; Lymphatic system; Metabolites; Mice; Optic Nerve; Retina; Vitreous Body; β-Amyloid
• ISSN: 1946-6234; 1946-6242; 1946-3242
• DOI: 10.1126/scitranslmed.aaw3210

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. β-amyloid (Aβ) 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 Aβ 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, Aβ 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.