Progress on Brain and Ocular Lymphatic System

Abstract

In recent years, 2 major discoveries have modified the traditional understanding of the brain. First, meningeal lymphatic vessels (MLV) were found in the dural sinus, which may absorb and drain cerebrospinal fluid (CSF). Second, the glymphatic system was discovered, composed of para-arterial CSF influx channel, paravenous interstitial fluid (ISF) efflux channel, and the water channel aquaporin-4 (AQP4) in astrocytes connecting the 2 channels. Accumulating evidence demonstrates that the lymphatic system of the brain plays a vital role within the circulation of CSF and, therefore, in the removal of metabolites. Therefore, it is involved in the incidence and development of some central nervous system (CNS) diseases. The optic nerve and retina are the extension of the CNS in the orbit. Whether they have a lymphatic system and how they clear the metabolites of the optic nerve and retina are still unclear. Recent studies have found that the ocular lymphatic system has a crucial impact on bounding eye diseases, like disorders of the optic nerve and retina. Therefore, here we review the recent research progress concerning the structure and function of MLV and glymphatic system. We also discuss the biomarkers for identification of lymphatic vessels, the composition of ocular lymphatic systems, and the possible association with diseases.

Lymphatic vessel: Origin, heterogeneity, biological functions and therapeutic targets

“…Although the brain parenchyma is devoid of lymphatic vessels, the rapid clearance of cellular debris and metabolic products in the central nervous system is attributable to the glymphatic system and meningeal lymphatic vessels. 103 The glymphatic system is composed of three essential components: the para-arterial cerebrospinal fluid influx channel, the para-venous interstitial fluid efflux channel, and the water channel aquaporin-4 in astrocytes that connect these channels. 103 Cerebrospinal fluid flows into the brain through the para-arterial space and exchanges with interstitial fluid via aquaporin-4; this type of exchange drives metabolite and interstitial fluid into the para-venous space and then into the cerebrospinal fluid circulatory system or directly through the capillary lymphatics into the cervical lymphatics.…”

“… 103 The glymphatic system is composed of three essential components: the para-arterial cerebrospinal fluid influx channel, the para-venous interstitial fluid efflux channel, and the water channel aquaporin-4 in astrocytes that connect these channels. 103 Cerebrospinal fluid flows into the brain through the para-arterial space and exchanges with interstitial fluid via aquaporin-4; this type of exchange drives metabolite and interstitial fluid into the para-venous space and then into the cerebrospinal fluid circulatory system or directly through the capillary lymphatics into the cervical lymphatics. In particular, the glymphatic system transports lipids within the brain.…”

Impact of Manipulative Treatment on Professional Drivers

“…It is still unclear whether they have a lymphatic system and how they eliminate metabolites from the optic nerve and retina. Recent studies have found that the ocular lymphatic system has a crucial impact on ocular diseases, such as optic nerve and retinal disorders [4].…”

Breaking a Vicious Circle: Lymphangiogenesis as a New Therapeutic Target in Wound Healing

“…Nevertheless, recent reports have confirmed the presence of meningeal lymphatic vessels (MLV) in the dura mater [ 2 , 5 ] and the existence of prelymphatic channels connected to the perivascular space able to drain effectively the interstitial fluid and assure the cleaning of the cerebral interstitial environment, the so-called glymphatic system [ 6 ]. Finally, even the retina [ 7 , 8 , 9 ], optic nerve [ 9 , 10 , 11 ], and conjunctive region [ 9 , 12 , 13 ] present MVL or glymphatic systems.…”

“…Interestingly, the exchange and removal of metabolites have shown great value and significance in the study of central nervous system diseases such as Alzheimer’s and subarachnoid hemorrhage, highlighting the importance of the lymphatic system in the central nervous system as well [ 9 ].…”