Abstract
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 intraocular pressure (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 |
|---|---|
| Journal | Investigative Ophthalmology & Visual Science |
| Publication status | Published - 2025 |
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 grant number EP/P024270/1. PSS acknowledges funding from EPSRC grant numbers EP/N014642/1, EP/S030875/1 and EP/T017899/1. The work presented herein 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 (grant numbers EP/N032861/1, EP/N032934/1, EP/P000851/1, EP/N032411/1, EP/N032152/1). We 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 grant number EP/V521929/1).
| Funders | Funder number |
|---|---|
| Engineering and Physical Sciences Research Council | EP/P024270/1, EP/N014642/1, EP/S030875/1, EP/T017899/1., EP/N032861/1, EP/N032934/1, EP/P000851/1, EP/N032411/1, EP/N032152/1, EP/V521929/1 |
Keywords
- Mathematical Modeling, aqueous humor, Unconventional outflow, glaucoma, medications, prostaglandins
ASJC Scopus subject areas
- Applied Mathematics
- Modelling and Simulation
- Ophthalmology
- Physiology (medical)
