Figure 1.

Schematic of major clearance systems in (A,B,C,F) the brain and (D,E,F) the eye. (A,B,C) are representations of the IPAD and glymphatic pathways; (A) is a cross-section of an arteriole and represents CSF flow (cyan arrows) from the SAS into the peri-arterial space, as well as ISF flow (green arrows) through the smooth muscle basement membranes; (B) is a cross-section of an arteriole transitioning into a capillary, where CSF exits the peri-arterial space via AQP4 water channels (purple) located on the astrocytic endfeet before mixing with ISF (cyan green arrow) and entering the smooth muscle basement membranes; (C) is a coronal cross-section through the head and represents the glymphatic pathway, dorsal mLVs, and CSF flow through an AG. CSF flows from the SAS into peri-arterial spaces before flowing into the brain parenchyma via AQP4 channels, mixing with ISF, and then entering the perivenous space for drainage via a convective flow. Fluid from the SAS can then drain into the mLVs (green openings) surrounding the SSS; (D) represents a cross-section of the anterior chamber of the eye. Cyan arrows represent production and flow of aqueous humor from the ciliary body. Red arrow represents the trabecular meshwork pathway where aqueous humor flows into the episcleral vein by passing through the Schlemm’s canal (blue opening). Green arrow represents the uveoscleral pathway where aqueous humor flows through the interstitial trabeculae of the ciliary bodies and enters the suprachoroidal space; (E) represents a cross-section of the optic nerve head. Müller cells within the retina, which share similar functions to astrocytes in the brain, are represented in dark green, with appendages that wrap around retinal capillaries (red dots), constituting part of the blood-retinal barrier. The broad stripe behind the Müller cells represents the INL. The optic nerve is surrounded by SAS through which CSF flows into the optic nerve; (F) is a diagram of CSF flow within the SAS, originating from the choroid plexus (orange) within the ventricles, as well as dorsal and basal mLVs. These mLVs travelling alongside the TS and SS, exiting out of the jugular foramen with the internal jugular vein, and draining into the deep cervical lymph nodes. Preauricular [1], submandibular [2], superficial cervical [3], deep cervical [4], and supraclavicular [5] lymph nodes are illustrated. IPAD, intramural periarterial drainage; CSF, cerebrospinal fluid; SAS, subarachnoid space; ISF, interstitial fluid; AQP4, aquaporin-4; mLVs, meningeal lymphatic vessels; AG, arachnoid granulation; SSS, superior sagittal sinus; INL, inner nuclear layer; TS, transverse sinuses; SS, sigmoid sinuses.