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

被引：168

作者：

Wang, Xiaowei ^{[1
,2
]}

Lou, Nanhong ^{[2
]}

Eberhardt, Allison ^{[2
]}

Yang, Yujia ^{[3
,4
]}

Kusk, Peter ^{[1
]}

Xu, Qiwu ^{[2
]}

Forstera, Benjamin ^{[5
,6
]}

Peng, Sisi ^{[2
]}

Shi, Meng ^{[3
,4
]}

Ladron-de-Guevara, Antonio ^{[2
]}

Delle, Christine ^{[1
]}

Sigurdsson, Bjorn ^{[1
]}

Xavier, Anna L. R. ^{[1
]}

Erturk, Ali ^{[5
,6
]}

Libby, Richard T. ^{[7
]}

Chen, Lu ^{[3
,4
]}

Thrane, Alexander S. ^{[1
,8
]}

Nedergaard, Maiken ^{[1
,2
]}

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

[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

[5] Ludwig Maximilians Univ Munich LMU, Inst Stroke & Dementia Res, Klinikum Univ Munchen, D-81377 Munich, Germany

[6] Helmholtz Ctr Munchen, ITERM, D-85764 Munich, Germany

[7] Univ Rochester, Med Ctr, Dept Ophthalmol, Rochester, NY 14642 USA

[8] Haukeland Hosp, Dept Ophthalmol, Jonas Lies Vei 65, N-5021 Bergen, Norway

来源：

SCIENCE TRANSLATIONAL MEDICINE | 2020年 / 12卷 / 536期

基金：

欧洲研究理事会;

关键词：

OPTIC-NERVE HEAD; GANGLION-CELL DEGENERATION; INTRAOCULAR-PRESSURE; MOUSE MODEL; INTRACRANIAL-PRESSURE; LAMINA-CRIBROSA; DISC EDEMA; GLAUCOMA; BRAIN; FLUID;

D O I：

10.1126/scitranslmed.aaw3210

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页数：14

共 90 条

[1] Human and nonhuman primate meninges harbor lymphatic vessels that can be visualized noninvasively by MRI [J].