Fabrizio Magonio
In 2012, Iliff, et al., described a bidirectional, polarized, paravascular fluid transport system in the brain, termed the “glymphatic system”, responsible for the clearance of metabolic waste. This system, mediated by astrocytes and aquaporin-4 channels, has been supported by experimental and imaging studies in animal models and, indirectly, in humans. Evidence in humans comes from imaging studies showing cerebrospinal fluid movement within the brain parenchyma, as well as anatomical observations. Since the eye is a diencephalic evagination and the retina is a part of the central nervous system, increasing attention has been directed towards the possibility of a similar clearance mechanism within the eye. The retina, being one of the most metabolically active tissues, requires efficient removal of neurotoxic waste. Recent experimental evidence suggests the existence of fluid transport pathways connecting the retina, optic nerve and cerebrospinal fluid compartments, potentially contributing to an ocular glymphatic system. Although the exact mechanisms remain incompletely understood, alterations in this system may play a role in the pathogenesis of ocular neurodegenerative diseases, including chronic open-angle glaucoma and age-related macular degeneration, conditions that share many similarities with Alzheimer’s disease. This review summarizes current knowledge on ocular hydrodynamics and discusses the emerging concept of the ocular glymphatic system, with particular attention to its potential physiological role and clinical implications. The possible influence of sleep and ocular motility on glymphatic clearance is also explored as a hypothesis requiring further investigation.