Review of a new concept of glaucoma pathogenesis based on the glymphatic theory of cerebrospinal fluid circulation

Abstract

General aspects of glaucoma: Glaucoma is a heterogeneous multi-factorial disease that is one of the main causes of blindness, along with degeneration of retinal ganglion cells and optic nerve atrophy.

Theories of pathogenesis: There are three theories of glaucoma pathogenesis: biomechanical, vascular, and biochemical.

Basic theory of the glymphatic system: The classical knowledge of cerebrospinal fluid circulation has been revised, and in 2012 a new concept of glial-perivascular – glymphatic perfusion of the brain parenchyma was introduced. Due to experimental and clinical studies, it is approved by many scientists, especially in relation to Alzheimer’s disease (AD), in which amyloid pathology is the result of dysfunction of the para-/perivascular transport/cleansing pathways.

Features of the optic nerve and the cribriform plate: The cribriform plate forms a barrier at the border of intraocular (IOP) and intracranial (ICP) pressures, thus affecting the para-/periarterial flow of cerebrospinal fluid to the optic nerve and retina, as well as the para-/perivenous cleansing outflow.

Morphofunctional evidence of an ocular glymphatic system: The presence of an ocular glymphatic system is con­firmed by in vivo experiments with the transfer of labeled substances through para-/perivascular structures from the ventricular or subarachnoid space to the optic nerve and by postmortem morphology.

Clinical evidence for the glymphatic system hypothesis: There is some clinical, including case-based, and epidemio­logical evidence for similarities between glaucomatous optic nerve/retinal injuries and AD, since both occur in the form of improper secretion of neurotoxic metabolites, and both are often diagnosed together.