title: Fast circulation of cerebrospinal fluid: an alternative perspective on the protective role of high intracranial pressure in ocular hypertension.
abstract: As ocular hypertension refers to a condition in which the intraocular pressure is consistently elevated but without development of glaucoma, study of it may provide important clues to factors that may play a protective role in glaucoma. β-amyloid, one of the key histopathological findings in Alzheimer's disease, has been reported to increase by chronic elevation of intraocular pressure in animals with experimentally induced ocular hypertension and to cause retinal ganglion cell death, pointing to similarities in molecular cell death mechanisms between glaucoma and Alzheimer's disease. On the other hand, recent studies have reported that intracranial pressure is higher in patients with ocular hypertension compared with controls, giving rise to the idea that elevated intracranial pressure may provide a protective effect for the optic nerve by decreasing the trans-lamina cribrosa pressure difference. The speculation that the higher intracranial pressure reported in ocular hypertension patients may protect against glaucoma mainly through a lower trans-lamina cribrosa pressure difference remains at least questionable. Here, we present an alternative viewpoint, according to which the protective effect of higher intracranial pressure could be due, at least in part, to a pressure-independent mechanism, namely faster cerebrospinal fluid production leading to increased cerebrospinal fluid turnover with enhanced removal of potentially neurotoxic waste products that accumulate in the optic nerve. This suggests a new hypothesis for glaucoma, which, just like Alzheimer's disease, may be considered then as an imbalance between production and clearance of neurotoxins, including β-amyloid. If confirmed, then strategies to improve cerebrospinal fluid flow are reasonable and could provide a new therapeutic approach for stopping the neurotoxic β-amyloid pathway in glaucoma.
authors.affiliation: Department of Psychiatry, PC Sint-Amandus, Beernem, Belgium. wostyn.peter@skynet.be.
authors.forename: Peter
authors.initials: P
authors.lastname: Wostyn
authors.affiliation: Department of Ophthalmology, Antwerp University Hospital, Antwerp, Belgium.
authors.forename: Veva
authors.initials: V
authors.lastname: De Groot
authors.affiliation: Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, University of Antwerp, Department of Biomedical Sciences, Antwerp, Belgium.
authors.forename: Debby
authors.initials: D
authors.lastname: Van Dam
authors.affiliation: Department of Psychiatry, Ghent University Hospital, Ghent, Belgium.
authors.forename: Kurt
authors.initials: K
authors.lastname: Audenaert
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, University of Antwerp, Department of Biomedical Sciences, Antwerp, Belgium.|Department of Neurology and Memory Clinic, Middelheim General Hospital, 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: D016229:Amyloid beta-Peptides / Q000502:physiology; D005901:Glaucoma / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D006801:Humans; D007427:Intracranial Pressure; D009798:Ocular Hypertension / Q000134:cerebrospinal fluid*; D009900:Optic Nerve / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000473:pathology*
chemical_list: D016229:Amyloid beta-Peptides
keywords: Alzheimer's disease; cerebrospinal fluid clearance; glaucoma; intracranial pressure; ocular hypertension