Glymphatic stasis at the site of the lamina cribrosa as a potential mechanism underlying open‐angle glaucoma. (27th February 2017)

• Record Type: Journal Article
• Authors: Wostyn, Peter; Killer, Hanspeter Esriel; De Deyn, Peter Paul
• Is Part Of: Clinical & experimental ophthalmology. Volume 45:Number 5(2017)
• Page Start: 539
• Page End: 547
• Publication Date: 2017-02-27
• Subjects: glaucoma -- intracranial pressure -- intraocular pressure -- lamina cribrosa -- trans‐lamina cribrosa pressure difference; Ophthalmology -- Periodicals; 617.7
• DOI: 10.1111/ceo.12915
• Languages: English
• ISSNs: 1442-6404

Abstract

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.