Optic Nerve Cerebrospinal Fluid Drained-out via Its Sheath Lymphatic Vessels

Abstract The cerebrospinal fluid (CSF) surrounding the optic nerve (to differentiate with the intracranial CSF, it is named as optic nerve CSF) plays important roles in nutrient exchange, waste removal, and maintenance of optic nerve function. Recent studies have suggested that the optic disc edema observed in astronauts may be linked to the retention of CSF around the optic nerve, and this retention may even be derived from impaired drainage of optic nerve CSF. However, how the optic nerve CSF is drained out remains inconclusive. We speculated that the optic nerve CSF may be drained out through lymphatic vessels of the optic nerve sheath. Here, we found by immunofluorescence and in vivo fluorescence imaging that, in both rats and humans, the optic nerve sheath has lymphatic vessels. Furthermore, we observed that the pressure in the optic nerve CSF is lower than the intracranial pressure, and the optic nerve CSF does not reflux into the intracranial space but is, instead, drained out into the deep cervical lymph nodes (dcLNs) through the lymphatic vessels in the optic nerve sheath. These observations have significant implications for understanding the physiological turnover and drainage pathways of optic nerve CSF. It may also help better understand the pathogenesis underlying spaceflight and Spaceflight Associated Neuro-Ocular Syndrome (SANS).