Age- and glaucoma-induced changes to the ocular glymphatic system

Xiaowei Wang; Christine Delle; Weiguo Peng; Virginia Plá; Michael Giannetto; Peter Kusk; Björn Sigurdsson; Shinya Sakurai; Amanda Sweeney; Qian Sun; Ting Du; Richard T. Libby; Maiken Nedergaard

Neurobiology of Disease (Nov 2023)

Age- and glaucoma-induced changes to the ocular glymphatic system

Xiaowei Wang,
Christine Delle,
Weiguo Peng,
Virginia Plá,
Michael Giannetto,
Peter Kusk,
Björn Sigurdsson,
Shinya Sakurai,
Amanda Sweeney,
Qian Sun,
Ting Du,
Richard T. Libby,
Maiken Nedergaard

Affiliations

Xiaowei Wang: Center for Translational Neuromedicine, Faculty of Medical and Health Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen N, Denmark; Center for Translational Neuromedicine, University of Rochester Medical School, Elmwood Avenue 601, Rochester, NY 14642, USA; Corresponding authors at: Center for Translational Neuromedicine, Faculty of Medical and Health Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen N, Denmark.
Christine Delle: Center for Translational Neuromedicine, Faculty of Medical and Health Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen N, Denmark
Weiguo Peng: Center for Translational Neuromedicine, Faculty of Medical and Health Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen N, Denmark; Center for Translational Neuromedicine, University of Rochester Medical School, Elmwood Avenue 601, Rochester, NY 14642, USA
Virginia Plá: Center for Translational Neuromedicine, Faculty of Medical and Health Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen N, Denmark
Michael Giannetto: Center for Translational Neuromedicine, University of Rochester Medical School, Elmwood Avenue 601, Rochester, NY 14642, USA; Neuroscience Graduate Program, University of Rochester Medical School, Elmwood Avenue 601, Rochester, NY 14642, USA
Peter Kusk: Center for Translational Neuromedicine, Faculty of Medical and Health Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen N, Denmark
Björn Sigurdsson: Center for Translational Neuromedicine, Faculty of Medical and Health Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen N, Denmark
Shinya Sakurai: Center for Translational Neuromedicine, University of Rochester Medical School, Elmwood Avenue 601, Rochester, NY 14642, USA
Amanda Sweeney: Center for Translational Neuromedicine, University of Rochester Medical School, Elmwood Avenue 601, Rochester, NY 14642, USA
Qian Sun: Center for Translational Neuromedicine, University of Rochester Medical School, Elmwood Avenue 601, Rochester, NY 14642, USA
Ting Du: Center for Translational Neuromedicine, University of Rochester Medical School, Elmwood Avenue 601, Rochester, NY 14642, USA
Richard T. Libby: Department of Ophthalmology, University of Rochester Medical Center, Elmwood Avenue 601, Rochester, NY 14642, USA
Maiken Nedergaard: Center for Translational Neuromedicine, Faculty of Medical and Health Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen N, Denmark; Center for Translational Neuromedicine, University of Rochester Medical School, Elmwood Avenue 601, Rochester, NY 14642, USA; Corresponding authors at: Center for Translational Neuromedicine, Faculty of Medical and Health Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen N, Denmark.

Journal volume & issue: Vol. 188
p. 106322

Abstract

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The ocular glymphatic system supports bidirectional fluid transport along the optic nerve, thereby removes metabolic wastes including amyloid-β. To better understand this biological process, we examined the distributions of intravitreally and intracisternally infused tracers in full-length optic nerves from different age groups of mice. Aging was linked to globally impaired ocular glymphatic fluid transport, similar to what has seen previously in the brain. Aging also reduced the pupillary responsiveness to light stimulation and abolished light-induced facilitation in anterograde ocular glymphatic flow. In contrast to normal aging, in the DBA/2 J model of glaucoma, we found a pathological increase of glymphatic fluid transport to the anterior optic nerve that was associated with dilation of the perivascular spaces. Thus, aging and glaucoma have fundamentally different effects on ocular glymphatic fluid transport. Manipulation of glymphatic fluid transport might therefore present a new target for the treatment of glaucoma.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

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