Abstract
PURPOSE: To develop a mathematical model of the unconventional outflow pathway.
METHODS: The unconventional pathway is modeled as having two key components: the uveo-vortex and the trans-scleral pathways. The uveo-vortex pathway is modeled using Starling's law and the trans-scleral flow using predominately hydrostatic forces. We include transcytosis from the choriocapillaris (CC) and collapsibility of the suprachoroidal space (SCS) as particular features. There is considerable uncertainty in a number of model parameter values, and we identify the most significant ones using sensitivity analysis.
RESULTS: The model successfully generates a fluid flow from anterior to posterior in the choroidal tissue and the SCS, which also demonstrates many of the known physiological features, including the insensitivity of the unconventional flow to fluctuations in the IOP, albumin removal by the trans-scleral flow, and the CC as a net absorber of fluid from, and supplier of albumin to, the choroidal tissue. The model supports the two previously proposed mechanisms of the action of prostaglandin F2α analogues.
CONCLUSIONS: We have developed a theoretical model of the unconventional aqueous outflow pathway that successfully captures its physiological features and elucidates the actions of prostaglandin F2α analogues and other drugs.
| Original language | English |
|---|---|
| Article number | 75 |
| Pages (from-to) | 75 |
| Journal | Investigative Ophthalmology & Visual Science |
| Volume | 66 |
| Issue number | 4 |
| Early online date | 28 Apr 2025 |
| DOIs | |
| Publication status | Published - 30 Apr 2025 |
Bibliographical note
Publisher Copyright:Copyright 2025 The Authors.
Funding
JHT acknowledges support from a Daphne Jackson Fellowship sponsored by the Royal Society and an Emmy Noether Fellowship from the London Mathematical Society, and is grateful to both these organisations for supporting her. She started work on this problem while based at Imperial College London. DRO acknowledges support from the BrightFocus Foundation (G2015145). TAS and PSS acknowledge funding from EPSRC (EP/P024270/1). PSS acknowledges funding from EPSRC (EP/N014642/1, EP/S030875/1 and EP/T017899/1). This work arose from problems presented at a study group funded by the Macular Society, and a study group funded by the EPSRC-funded UK Fluids Network (EP/N032861/1, EP/N032934/1, EP/P000851/1, EP/N032411/1, EP/N032152/1). The authors are grateful to both the Macular Society and the UK Fluids Network for supporting this research. The work has also been supported by the Isaac Newton Institute (funded by EPSRC EP/V521929/1).
| Funders | Funder number |
|---|---|
| London Mathematical Society | |
| Imperial College London | |
| Macular Society | |
| Royal Society | |
| Engineering and Physical Sciences Research Council | EP/P000851/1, EP/N032934/1, EP/N032861/1, EP/S030875/1, EP/P024270/1, EP/T017899/1, EP/N032152/1, EP/N032411/1, EP/N014642/1 |
| BrightFocus Foundation | G2015145 |
| Isaac Newton Institute for Mathematical Sciences | EP/V521929/1 |
Keywords
- Aqueous Humor/metabolism
- Sclera/physiology
- Humans
- Intraocular Pressure/physiology
- Choroid/physiology
- Models, Biological
- Models, Theoretical
- Uvea/physiology
- aqueous humor
- glaucoma medications
- mathematical modeling
- prostaglandins
- unconventional outflow
ASJC Scopus subject areas
- Applied Mathematics
- Modelling and Simulation
- Ophthalmology
- Physiology (medical)
- Sensory Systems
- Cellular and Molecular Neuroscience
Access to Document
- unconv-paper-revision2-unmarked
For the purpose of open access, the author has applied a Creative Commons Attribution (CC-BY) licence to any Author Accepted Manuscript version arising.