Reply

Abstract

We thank Wostyn et al for their comments regarding our article. 1 As our results suggest an altered translamina cribrosa pressure difference between the brain and the eye, we share the view that translamina cribrosa glymphatic outflow from the eye to the optic nerve and optic nerve sheath may be altered in microgravity. As indicated in the animal study by Wang et al, the eye's glymphatic system is likely involved in removing metabolites from neural activity from the intraocular space through the optic nerve head to the optic nerve subarachnoid space. 2 Importantly, the study also suggests that stimulating pupil constrictions by cyclic light pulses, which increases aqueous outflow and likely creates pressure transients in the eye, may counterbalance some of the negative effects of an altered pressure gradient. 2 If spaceflight associated neuro-ocular syndrome (SANS) can be shown to be related to reduced ocular glymphatic flow, in addition to optic nerve elongation, this gives hope that easily implemented interventions such as sessions of mechanically elevated intraocular pressure and/or light-based stimulation may prove important in remedying SANS. Owing to its dependency on the translamina cribrosa pressure difference, the understanding of this glymphatic flow route will likely be further complicated by factors such as optic nerve compartmentalization, which could potentially occur either owing to optic nerve sheath collapse related to posture-induced pressure gradients, 3,4 or from edema-related narrowing of the optic nerve subarachnoid space, 5 highlighting the need of more research in this area. In summary, we agree that studying the translamina cribrosa glymphatic outflow from the eye to optic nerve and optic nerve sheath may provide new information needed for understanding SANS. The generated knowledge may also be relevant for terrestrial diseases of the optic nerve and optic nerve head, such as glaucoma and idiopathic intracranial hypertension.