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.

Neuroprotective properties of Na+/H+-exchanger isoform-1 inhibitor in experimental POAG

“…The IOP level in laboratory animals was determined using an Icare ® TONOVET tonometer (Finland) (Dolzhikov et al 2020).…”

Functional and clinical morphology of Virchow-Robin spaces: from the discovery up to the newest theories

“…В клинических исследованиях периваскулярные пространства (ПВП) получили наибольшее внимание в связи с проблемой, названной «болезнью малых сосудов». Последняя по имеющимся определениям представляет широкую и неоднородную группу патологических процессов, общим для которых является поражение внутримозговых и/или субарахноидальных сосудов, включая мелкие артерии, вены и звенья микроциркуляторного русла [8,26]. В нее по этиопатогенетическому принципу включены артериосклероз ассоциированный с возрастом или артериальной гипертензией (гипертензивная артериопатия), также определяемая как спорадическая неамилоидная ангиопатия, различные варианты амилоидной ангиопатии, субкортикальные инфаркты, лейкоэнцефалопатия [26].…”