Optimal control with MANF treatment of photoreceptor degeneration

• Published in: Mathematical medicine and biology Vol. 37; no. 1; p. 1
• Main Authors: Camacho, Erika T, Lenhart, Suzanne, Melara, Luis A, Villalobos, M Cristina, Wirkus, Stephen
• Format: Journal Article
• Language: English
• Published: England 28.02.2020
• Subjects: Animals; Apoptosis - drug effects; Apoptosis - physiology; Computer Simulation; Disease Models, Animal; Humans; Macular Degeneration - drug therapy; Macular Degeneration - pathology; Macular Degeneration - physiopathology; Mathematical Concepts; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Models, Neurological; Nerve Degeneration - drug therapy; Nerve Degeneration - pathology; Nerve Degeneration - physiopathology; Nerve Growth Factors - physiology; Nerve Growth Factors - therapeutic use; Photoreceptor Cells, Vertebrate - drug effects; Photoreceptor Cells, Vertebrate - pathology; Photoreceptor Cells, Vertebrate - physiology; Retinal Cone Photoreceptor Cells - drug effects; Retinal Cone Photoreceptor Cells - pathology; Retinal Cone Photoreceptor Cells - physiology; Retinal Rod Photoreceptor Cells - drug effects; Retinal Rod Photoreceptor Cells - pathology; Retinal Rod Photoreceptor Cells - physiology; Retinitis Pigmentosa - drug therapy; Retinitis Pigmentosa - pathology; Retinitis Pigmentosa - physiopathology; model of ordinary differential equations; apoptosis; optimal control; mesencephalic astrocyte-derived neurotrophic factor; photoreceptor degeneration
• ISSN: 1477-8602
• DOI: 10.1093/imammb/dqz003

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.