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.
基金:
European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme [742112]; Novo Nordisk; Lundbeck Foundations; Dr. Miriam and Sheldon G. Adelson Medical Research Foundation; NIH/NINDS/NIA/NEI [R01NS100366, RF1AG057575, R01EY028995]; Research to Prevent Blindness Foundation (Research to Prevent Blindness Stein Innovation Award); Cure Alzheimer's Fund; Western Norway Regional Health Authority (Helse Vest grant) [912179, 912230]; Norwegian Glaucoma Research Foundation; European Research Council (ERC) [742112] Funding Source: European Research Council (ERC)
第一作者机构:[1]Univ Copenhagen, Ctr Translat Neuromed, Fac Med & Hlth Sci, Blegdamsvej 3B, DK-2200 Copenhagen N, Denmark[2]Univ Rochester, Sch Med, Ctr Translat Neuromed, Elmwood Ave 601, Rochester, NY 14642 USA
通讯作者:
通讯机构:[1]Univ Copenhagen, Ctr Translat Neuromed, Fac Med & Hlth Sci, Blegdamsvej 3B, DK-2200 Copenhagen N, Denmark[*1]Univ Copenhagen, Ctr Translat Neuromed, Fac Med & Hlth Sci, Blegdamsvej 3B, DK-2200 Copenhagen N, Denmark[2]Univ Rochester, Sch Med, Ctr Translat Neuromed, Elmwood Ave 601, Rochester, NY 14642 USA[*2]Univ Rochester, Sch Med, Ctr Translat Neuromed, Elmwood Ave 601, Rochester, NY 14642 USA[3]Univ Calif Berkeley, Ctr Eye Dis & Dev, Vis Sci Grad Program, Berkeley, CA 94720 USA[*3]Univ Calif Berkeley, Ctr Eye Dis & Dev, Vis Sci Grad Program, Berkeley, CA 94720 USA[4]Univ Calif Berkeley, Sch Optometry, Berkeley, CA 94720 USA[*4]Univ Calif Berkeley, Sch Optometry, Berkeley, CA 94720 USA
推荐引用方式(GB/T 7714):
Wang Xiaowei,Lou Nanhong,Eberhardt Allison,et al.An ocular glymphatic clearance system removes β-amyloid from the rodent eye[J].SCIENCE TRANSLATIONAL MEDICINE.2020,12(536):eaaw3210.doi:10.1126/scitranslmed.aaw3210.
APA:
Wang, Xiaowei,Lou, Nanhong,Eberhardt, Allison,Yang, Yujia,Kusk, Peter...&Nedergaard, Maiken.(2020).An ocular glymphatic clearance system removes β-amyloid from the rodent eye.SCIENCE TRANSLATIONAL MEDICINE,12,(536)
MLA:
Wang, Xiaowei,et al."An ocular glymphatic clearance system removes β-amyloid from the rodent eye".SCIENCE TRANSLATIONAL MEDICINE 12..536(2020)