Optimal control with MANF treatment of photoreceptor degeneration

Erika T. Camacho, Suzanne Lenhart, Luis A. Melara, M. Cristina Villalobos, Stephen Wirkus

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

People afflicted with diseases such as retinitis pigmentosa and age-related macular degeneration experience a decline in vision due to photoreceptor degeneration, which is currently unstoppable and irreversible. Currently there is no cure for diseases linked to photoreceptor degeneration. Recent experimental work showed that mesencephalic astrocyte-derived neurotrophic factor (MANF) can reduce neuron death and, in particular, photoreceptor death by reducing the number of cells that undergo apoptosis. In this work, we build on an existing system of ordinary differential equations that represent photoreceptor interactions and incorporate MANF treatment for three experimental mouse models having undergone varying degrees of photoreceptor degeneration. Using MANF treatment levels as controls, we investigate optimal control results in the three mouse models. In addition, our numerical solutions match the experimentally observed surviving percentage of photoreceptors and our uncertainty and sensitivity analysis identifies significant parameters in the math model both with and without MANF treatment.

Original languageEnglish (US)
Pages (from-to)1-21
Number of pages21
JournalMathematical Medicine and Biology
Volume37
Issue number1
DOIs
StatePublished - Feb 28 2020

Keywords

  • apoptosis
  • mesencephalic astrocyte-derived neurotrophic factor
  • model of ordinary differential equations
  • optimal control
  • photoreceptor degeneration

ASJC Scopus subject areas

  • Neuroscience(all)
  • Modeling and Simulation
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Environmental Science(all)
  • Pharmacology
  • Applied Mathematics

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