title: Glymphatic stasis at the site of the lamina cribrosa as a potential mechanism underlying open-angle glaucoma.
abstract: The underlying pathophysiology of primary open-angle glaucoma remains unclear, but the lamina cribrosa seems to be the primary site of injury, and raised intraocular pressure is a major risk factor. In recent years, a decreased intracranial pressure, leading to an abnormally high trans-lamina cribrosa pressure difference, has gained interest as a new risk factor for glaucoma. New research now lends support to the hypothesis that a paravascular transport system is present in the eye analogous to the recently discovered 'glymphatic system' in the brain, which is a functional waste clearance pathway that promotes elimination of interstitial solutes, including β-amyloid, from the brain along paravascular channels. Given that β-amyloid has been reported to increase by chronic elevation of intraocular pressure in glaucomatous animal models and to cause retinal ganglion cell death, the discovery of a paravascular clearance system in the eye may provide powerful new insights into the pathophysiology of primary open-angle glaucoma. In this review, we provide a new conceptual framework for understanding the pathogenesis of primary open-angle glaucoma, present supporting preliminary data from our own post-mortem study and hypothesize that the disease may result from restriction of normal glymphatic flow at the level of the lamina cribrosa owing to a low intracranial pressure and/or a high trans-lamina cribrosa pressure gradient. If confirmed, this viewpoint could offer new perspectives for the development of novel diagnostic and therapeutic strategies for this devastating disorder.
authors.affiliation: Department of Psychiatry, PC Sint-Amandus, Beernem, Belgium.
authors.forename: Peter
authors.initials: P
authors.lastname: Wostyn
authors.affiliation: Department of Ophthalmology, Kantonsspital Aarau, Aarau, Switzerland.
authors.forename: Hanspeter Esriel
authors.initials: HE
authors.lastname: Killer
authors.affiliation: Laboratory of Neurochemistry and Behavior. Institute Born-Bunge, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.|Department of Neurology and Memory Clinic, Middelheim General Hospital (ZNA), Antwerp, Belgium.|Department of Neurology and Alzheimer Research Center, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Peter Paul
authors.initials: PP
authors.lastname: De Deyn
mesh_terms: D000818:Animals; D015170:Cerebrospinal Fluid Pressure / Q000502:physiology*; D005902:Glaucoma, Open-Angle / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007429:Intraocular Pressure / Q000502:physiology*; D009898:Optic Disk / Q000473:pathology*; D012165:Retinal Ganglion Cells / Q000473:pathology*; D014065:Tonometry, Ocular
keywords: glaucoma; intracranial pressure; intraocular pressure; lamina cribrosa; trans-lamina cribrosa pressure difference