Biofluid modeling of the coupled eye-brain system and insights into simulated microgravity conditions

Abstract

This work aims at investigating the interactions between the flow of fluids in the eyes and the brain and their potential implications in structural and functional changes in the eyes of astronauts, a condition also known as spaceflight associated neuro-ocular syndrome (SANS). To this end, we propose a reduced (0-dimensional) mathematical model of fluid flow in the eyes and brain, which is embedded into a simplified whole-body circulation model. In particular, the model accounts for: (i) the flows of blood and aqueous humor in the eyes; (ii) the flows of blood, cerebrospinal fluid and interstitial fluid in the brain; and (iii) their interactions. The model is used to simulate variations in intraocular pressure, intracranial pressure and blood flow due to microgravity conditions, which are thought to be critical factors in SANS. Specifically, the model predicts that both intracranial and intraocular pressures increase in microgravity, even though their respective trends may be different. In such conditions, ocular blood flow is predicted to decrease in the choroid and ciliary body circulations, whereas retinal circulation is found to be less susceptible to microgravity-induced alterations, owing to a purely mechanical component in perfusion control associated with the venous segments. These findings indicate that the particular anatomical architecture of venous drainage in the retina may be one of the reasons why most of the SANS alterations are not observed in the retina but, rather, in other vascular beds, particularly the choroid. Thus, clinical assessment of ocular venous function may be considered as a determinant SANS factor, for which astronauts could be screened on earth and in-flight.

<p>Spaceflight Associated Neuro-Ocular Syndrome (SANS): A Systematic Review and Future Directions</p>

“…7 Aside from in vivo measurements, a mathematical model of fluid flow in the eyes and brain embedded into a simplified whole-body circulation model predicted raised ICP and IOP in microgravity. 19 This model predicted decreased ocular blood flow to the choroid and ciliary body whereas retinal circulation was found to be less susceptible to microgravity induced changes.…”

“…Aside from technology that could be used inflight, there are various reports of novel approaches to increase our understanding of SANS. Salerni et al 19 reported a mathematical model of fluid flow in the eyes and brain which predicted increased ICP and IOP in microgravity, as well as decreased ocular blood flow in the choroid and ciliary body. As noted above, the lymphatic system has been proposed to play a role in contributing to SANS, and Rasmussen et al 32 described a technique that could be used to further our understanding of this.…”

Neurodegenerative Disorders of the Eye and of the Brain: A Perspective on Their Fluid-Dynamical Connections and the Potential of Mechanism-Driven Modeling

“…The dynamics of blood, aqueous humor, and CSF in the eye and in the brain are intrinsically intertwined, with alterations in their flow rates and pressures being associated with several pathological conditions, including glaucoma, NDD and SANS, as discussed in section 2. The study of this complex system via mechanism-driven models is still in its infancy, with most investigations being motivated by research in glaucoma (Carichino et al, 2014;Harris et al, 2019;Sala, 2019;Sala et al, 2019b) and SANS (Nelson et al, 2017;Feola et al, 2018;Kaskar et al, 2019;Salerni et al, 2019).…”

Modeling a potential SANS countermeasure by experimental manipulation of the translaminar pressure difference in mice

“…Another example, normal tension glaucoma, occurs when IOP is again normal but ICP is reduced and the TLPD is increased, and results in optic nerve cupping and classic changes in vision [1][2][3][10][11][12][13] . Not surprisingly, several groups have suggested that IOP and ICP exist in a delicate balance, and that the manipulation of one pressure can counterbalance abnormalities in the other [14][15][16][17][18][19][20] . Unfortunately, the relative inaccessibility of directly measured ICP in humans, which requires either lumbar puncture or intracranial instrumentation, hinders the direct testing of these hypotheses, especially under conditions of microgravity 21 .…”

“…npj Microgravity (2020)19 Published in cooperation with the Biodesign Institute at Arizona State University, with the support of NASA1234567890():,;…”