Mathematical models of retinitis pigmentosa: the trophic factor hypothesis

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Abstract

Retinitis pigmentosa (RP) is the term used to denote a group of inherited retinal-degenerative conditions that cause progressive sight loss. Individuals with this condition lose their light-sensitive photoreceptor cells, known as rods and cones, over a period of years to decades; degeneration starting in the retinal periphery, and spreading peripherally and centrally over time. RP is a rod-cone dystrophy, meaning that rod health and function are affected earlier and more severely than that of cones. Rods degenerate due to an underlying mutation, whereas the reasons for cone degeneration are unknown. A number of mechanisms have been proposed to explain secondary cone loss and the spatio-temporal patterns of retinal degeneration in RP. One of the most promising is the trophic factor hypothesis, which suggests that rods produce a factor necessary for cone survival, such that, when rods degenerate, cone degeneration follows. In this paper we formulate and analyse mathematical models of human RP under the trophic factor hypothesis. These models are constructed as systems of reaction-diffusion partial differential equations in one spatial dimension, and are solved and analysed using a combination of numerical and analytical methods. We predict the conditions under which cones will degenerate following the loss of a patch of rods from the retina, the critical trophic factor treatment rate required to prevent cone degeneration following rod loss and the spatio-temporal patterns of cone loss that would result if the trophic factor mechanism alone were responsible for retinal degeneration.
Original languageEnglish
Article number110938
JournalJournal of Theoretical Biology
Volume534
Early online date20 Oct 2021
DOIs
Publication statusPublished - 7 Feb 2022

Bibliographical note

Funding Information:
P.A.R. is funded by BBSRC (BB/R014817/1) and thanks Tom Baden for allowing the time to pursue this research. P.A.R. also thanks the reviewers for their helpful and insightful comments.

Publisher Copyright:
© 2021 Elsevier Ltd

Keywords

  • Asymptotic analysis
  • Partial differential equations
  • Photoreceptors
  • Retina
  • Rod-derived cone viability factor

ASJC Scopus subject areas

  • Statistics and Probability
  • Modelling and Simulation
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)
  • Applied Mathematics

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