An ocular glymphatic clearance system removes beta-amyloid from the rodent eye
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An ocular glymphatic clearance system removes beta-amyloid from the rodent eye. / Wang, Xiaowei; Lou, Nanhong; Eberhardt, Allison; Yang, Yujia; Kusk, Peter; Xu, Qiwu; Forstera, Benjamin; Peng, Sisi; Shi, Meng; Ladron-de-Guevara, Antonio; Delle, Christine; Sigurdsson, Bjorn; Xavier, Anna L. R.; Erturk, Ali; Libby, Richard T.; Chen, Lu; Thrane, Alexander S.; Nedergaard, Maiken.
In: Science Translational Medicine, Vol. 12, No. 536, eaaw3210, 2020.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - An ocular glymphatic clearance system removes beta-amyloid from the rodent eye
AU - Wang, Xiaowei
AU - Lou, Nanhong
AU - Eberhardt, Allison
AU - Yang, Yujia
AU - Kusk, Peter
AU - Xu, Qiwu
AU - Forstera, Benjamin
AU - Peng, Sisi
AU - Shi, Meng
AU - Ladron-de-Guevara, Antonio
AU - Delle, Christine
AU - Sigurdsson, Bjorn
AU - Xavier, Anna L. R.
AU - Erturk, Ali
AU - Libby, Richard T.
AU - Chen, Lu
AU - Thrane, Alexander S.
AU - Nedergaard, Maiken
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
U2 - 10.1126/scitranslmed.aaw3210
DO - 10.1126/scitranslmed.aaw3210
M3 - Journal article
C2 - 32213628
VL - 12
JO - Science Translational Medicine
JF - Science Translational Medicine
SN - 1946-6234
IS - 536
M1 - eaaw3210
ER -
ID: 239301378