The brain – eye transport pathway anatomy and AQP4-mediated glymphatic mechanism in AD-related retinal disorders. (A) Anatomy of the brain–eye transport pathway. Brain–eye transport has three parts: transport along the SAS and optic nerve sheath, draining through optic nerve meningeal lymphatic vessels and periorbital lymphatic vessels. Second, transport along the myelinated axon spaces within the optic nerve toward the eye. Third, the transport of Aβ accumulated in the brain through the PVS of the CRA in the optic nerve, spreading to the retina. (B) Mechanism of AD-relevant retinal disease resulting from abnormal ocular glymphatic clearance by disrupted AQP4 polarity. In AD patients and 5×FAD mice, Aβ transported via the brain–eye pathway can enter the retina and accumulate through periarterial space in the short term. Over a longer duration, accumulated Aβ can be excreted through the perivenous space-optic nerve meningeal lymphatics pathway. During this process, the accumulated Aβ in the retina is transported from periarterial space to perivenous space and within the veins. Abnormal distribution of AQP4 in the PVS is a key factor causing abnormal accumulation of Aβ in the retina, subsequently triggering glial cell activation, inflammatory responses, retinal atrophy, and visual functional impairments.