Speaker
Description
The retina is the light-detecting tissue layer which lines the back of the eye. There is an increasing awareness of the central importance of metabolic dysfunction in driving a range of currently incurable blinding retinal conditions. The retinal metabolic network is highly nonlinear with multiple feedback mechanisms, necessitating a mathematical modelling approach to accompany ongoing experimental studies for full understanding. We developed a novel mathematical model of retinal metabolism to explore how the retina maintains healthy metabolic homeostasis and how this breaks down in disease.
An ordinary differential equation (ODE) model was formulated to describe and predict the evolving concentrations over time of respiratory metabolites in outer retinal cells. The model accounts for the passage and transformation of metabolites through key respiratory pathways. The model was parameterised using data from the literature and through fitting to data from ongoing experimental studies. The full model was solved computationally, while reduced models were solved analytically.
Our model demonstrates behaviour in agreement with experimental studies, showing metabolites moving through the metabolic pathways in the established fashion. Further, simulations predict key metabolites and processes for maintaining metabolic homeostasis, indicating potential treatment strategies where this breaks down in disease.
Bibliography
@Article{Roberts_2022b,
author = {Roberts, P. A.},
title = {Inverse Problem Reveals Conditions for Characteristic Retinal Degeneration Patterns in Retinitis Pigmentosa Under the Trophic Factor Hypothesis},
journal = {Front. Aging Neurosci.},
year = {2022b},
volume = {14},
pages = {765966},
doi = {https://doi.org/10.3389/fnagi.2022.765966},
}
@Article{Roberts_2022a,
author = {Roberts, P. A.},
title = {Mathematical Models of Retinitis Pigmentosa: The Trophic Factor Hypothesis},
journal = {J. Theor. Biol.},
year = {2022a},
volume = {534},
pages = {110938},
doi = {https://doi.org/10.1016/j.jtbi.2021.110938},
}
@Article{Roberts_et_al_2018a,
author = {Roberts, P. A. and Gaffney, E. A. and Whiteley, J. P. and Luthert, P. J. and Foss, A. J. E. and Byrne, H. M.},
title = {Predictive Mathematical Models for the Spread and Treatment of Hyperoxia-induced Photoreceptor Degeneration in Retinitis Pigmentosa},
journal = {Invest. Ophthalmol. Vis. Sci.},
year = {2018},
volume = {59},
number = {3},
pages = {1238-1249},
doi = {https://doi.org/10.1167/iovs.17-23177},
}
@Article{Roberts_et_al_2017,
author = {Roberts, P. A. and Gaffney, E. A. and Luthert, P. J. and Foss, A. J. E. and Byrne, H. M.},
title = {Mathematical models of retinitis pigmentosa: The oxygen toxicity hypothesis},
journal = {J. Theor. Biol.},
year = {2017},
volume = {425},
pages = {53-71},
doi = {https://doi.org/10.1016/j.jtbi.2017.05.006}
}
@Article{Roberts_et_al_2016a,
author = {Roberts, P. A. and Gaffney, E. A. and Luthert, P. J. and Foss, A. J. E. and Byrne, H. M.},
title = {Retinal oxygen distribution and the role of neuroglobin},
journal = {J. Math. Biol.},
year = {2016},
volume = {73},
number = {1},
pages = {1-38},
doi = {https://doi.org/10.1007/s00285-015-0931-y}
}
