Collaborative Research: Multiscale Modeling of Intraocular Pressure Dynamics and Its Role in Ocular Physiology and Pharmacology

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This project will develop quantitative methods to combat vision impairment, which is one of the most impactful factors affecting quality of life. Specifically, this project will study the pressure of the fluids filling the eye globe, also called intraocular pressure, whose control is crucial to maintain a proper visual function. Chronically high intraocular pressure is associated with high risk of developing glaucoma, a progressive optic neuropathy characterized by a loss of retinal ganglion cells and permanent vision loss. Glaucoma constitutes one of the leading causes of irreversible blindness worldwide. Despite the importance of maintaining healthy levels of intraocular pressure, to date, the question of what is its optimal range for a given individual remains unanswered. The variability in outcomes, side effects and hemodynamic impacts following medications that lower intraocular pressure in glaucoma patients poses an additional, and currently unresolved, challenge in preventing vision loss for millions of individuals. The PIs will address this critical need by utilizing the laws of physics to develop a virtual laboratory where the relationship between intraocular pressure, medications, hemodynamics and ocular function can be studied quantitatively, and the optimal target level for intraocular pressure and the therapeutic strategy to achieve it can be theoretically estimated by accounting for patient's specific conditions. The development of a virtual laboratory to study ocular physiology and function requires to account for multiple length scales simultaneously. Since the action of medications occurs at the cellular level (approx. length scale: 100 microns), even down to the ion exchangers across the membrane of the non-pigmented epithelial cells within the ciliary processes (approx. length scale: 10 nm), while the clinical assessments of ocular hemodynamics and function occur at the whole organ level (approx. length scale: 3cm), it is necessary to adopt a multiscale modeling approach. The main challenges of this project are: (i) capturing the essential biophysical features of ocular physiology across length scales that differ by 6 orders of magnitude, while maintaining the solution of the overall model affordable; (ii) preserving the essential biophysical features of ocular physiology when discretizing the multiscale problem in order to obtain its approximate numerical solution; (iii) validating the model predictions with a large and comprehensive clinical and experimental dataset. To best address these challenges and successfully complete this project, the model development is articulated into two specific aims: (Aim 1) Multiscale modeling of the relationship between aqueous humor flow and medications for intraocular pressure to theoretically investigate the hypotensive efficacy on patients presenting different clinical conditions; (Aim2) Multiscale modeling of the relationship between aqueous humor flow and ocular perfusion to theoretically investigate the changes on ocular hemodynamics and function in patients presenting different clinical conditions.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.