RT Journal Article
SR Electronic
T1 The Ocular Glymphatic Clearance System
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2019.12.29.889873
DO 10.1101/2019.12.29.889873
A1 Xiaowei Wang
A1 Nanhong Lou
A1 Allison Eberhardt
A1 Peter Kusk
A1 Qiwu Xu
A1 Benjamin Förstera
A1 Sisi Peng
A1 Yujia Yang
A1 Meng Shi
A1 Anna L. R. Xavier
A1 Ali Ertürk
A1 Richard T. Libby
A1 Lu Chen
A1 Alexander S. Thrane
A1 Maiken Nedergaard
YR 2019
UL http://biorxiv.org/content/early/2019/12/30/2019.12.29.889873.abstract
AB Despite high metabolic activity, the retina and optic nerve head lack traditional lymphatic drainage. We here identified a novel ocular glymphatic clearance route for fluid and wastes via the proximal optic nerve. Amyloid-β (Aβ) was cleared from the vitreous via a pathway 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, while 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 discovery of a novel pathway for removal of fluid and metabolites from the intraocular space prompts a reevaluation of the core principles governing eye physiology and provides a framework for new therapeutic approaches to treat common eye diseases, including glaucoma.One Sentence Summary Glymphatic pathway clears ocular amyloid-β via optic nerve and fails in glaucoma.