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Predictive mathematical models for the spread and treatment of hyperoxia-induced photoreceptor degeneration in retinitis pigmentosa

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Version 2 2023-06-12, 09:02
Version 1 2023-06-09, 17:14
journal contribution
posted on 2023-06-12, 09:02 authored by Paul Roberts, Eamonn A Gaffney, Jonathan P Whiteley, Philip J Luthert, Alexander J E Foss, Helen M Byrne
Purpose: To determine whether the oxygen toxicity hypothesis can explain the distinctive spatio-temporal patterns of retinal degeneration associated with human retinitis pigmentosa (RP) and to predict the effects of antioxidant and trophic factor treatments under this hypothesis. Methods: Three mathematical models were derived to describe the evolution of the retinal oxygen concentration and photoreceptor density over time. The first model considers only hyperoxia-induced degeneration, while the second and third models include mutation-induced rod and cone loss respectively. The models were formulated as systems of partial differential equations, defined on a two-dimensional domain spanning the region between the foveal center and the ora serrata, and were solved numerically using the finite element method. Results: The mathematical models recapitulate patterns of retinal degeneration which involve preferential loss of photoreceptors in the parafoveal/perifoveal and far-peripheral retina, while those which involve a preferential loss of midperipheral photoreceptors cannot be reproduced. Treatment with antioxidants or trophic factors is predicted to delay, halt, or partially reverse retinal degeneration, depending upon the strength and timing of treatment and disease severity. Conclusions: The model simulations indicate that while the oxygen toxicity hypothesis is sufficient to explain some of the patterns of retinal degeneration observed in human RP, additional mechanisms are necessary to explain the full range of behaviors. The models further suggest that antioxidant and trophic factor treatments have the potential to reduce hyperoxia-induced disease severity and that, where possible, these treatments should be targeted at retinal regions with low photoreceptor density to maximize their efficacy.

History

Publication status

  • Published

File Version

  • Published version

Journal

Investigative Ophthalmology & Visual Science

ISSN

1552-5783

Publisher

Association for Research in Vision and Ophthalmology

Issue

3

Volume

59

Page range

1238-1249

Department affiliated with

  • Neuroscience Publications

Research groups affiliated with

  • Sussex Neuroscience Publications

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2019-03-12

First Open Access (FOA) Date

2019-03-12

First Compliant Deposit (FCD) Date

2019-03-11

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