A Mathematical Analysis of Aerobic Glycolysis Triggered by Glucose Uptake in Cones

Erika Camacho, Danielle Brager, Ghizlane Elachouri, Tatyana Korneyeva, Géraldine Millet-Puel, José Alain Sahel, Thierry Léveillard

Research output: Contribution to journalArticle

Abstract

Patients affected by retinitis pigmentosa, an inherited retinal disease, experience a decline in vision due to photoreceptor degeneration leading to irreversible blindness. Rod-derived cone viability factor (RdCVF) is the most promising mutation-independent treatment today. To identify pathologic processes leading to secondary cone photoreceptor dysfunction triggering central vision loss of these patients, we model the stimulation by RdCVF of glucose uptake in cones and glucose metabolism by aerobic glycolysis. We develop a nonlinear system of enzymatic functions and differential equations to mathematically model molecular and cellular interactions in a cone. We use uncertainty and sensitivity analysis to identify processes that have the largest effect on the system and their timeframes. We consider the case of a healthy cone, a cone with low levels of glucose, and a cone with low and no RdCVF. The three key processes identified are metabolism of fructose-1,6-bisphosphate, production of glycerol-3-phosphate and competition that rods exert on cone resources. The first two processes are proportional to the partition of the carbon flux between glycolysis and the pentose phosphate pathway or the Kennedy pathway, respectively. The last process is the rods’ competition for glucose, which may explain why rods also provide the RdCVF signal to compensate.

Original languageEnglish (US)
Article number4162
JournalScientific reports
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2019

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Vertebrate Photoreceptor Cells
Glycolysis
Glucose
Retinal Cone Photoreceptor Cells
Carbon Cycle
Pentose Phosphate Pathway
Retinal Diseases
Molecular Models
Retinitis Pigmentosa
Pathologic Processes
Blindness
Uncertainty
Mutation
Therapeutics

ASJC Scopus subject areas

  • General

Cite this

Camacho, E., Brager, D., Elachouri, G., Korneyeva, T., Millet-Puel, G., Sahel, J. A., & Léveillard, T. (2019). A Mathematical Analysis of Aerobic Glycolysis Triggered by Glucose Uptake in Cones. Scientific reports, 9(1), [4162]. https://doi.org/10.1038/s41598-019-39901-z

A Mathematical Analysis of Aerobic Glycolysis Triggered by Glucose Uptake in Cones. / Camacho, Erika; Brager, Danielle; Elachouri, Ghizlane; Korneyeva, Tatyana; Millet-Puel, Géraldine; Sahel, José Alain; Léveillard, Thierry.

In: Scientific reports, Vol. 9, No. 1, 4162, 01.12.2019.

Research output: Contribution to journalArticle

Camacho, E, Brager, D, Elachouri, G, Korneyeva, T, Millet-Puel, G, Sahel, JA & Léveillard, T 2019, 'A Mathematical Analysis of Aerobic Glycolysis Triggered by Glucose Uptake in Cones', Scientific reports, vol. 9, no. 1, 4162. https://doi.org/10.1038/s41598-019-39901-z
Camacho, Erika ; Brager, Danielle ; Elachouri, Ghizlane ; Korneyeva, Tatyana ; Millet-Puel, Géraldine ; Sahel, José Alain ; Léveillard, Thierry. / A Mathematical Analysis of Aerobic Glycolysis Triggered by Glucose Uptake in Cones. In: Scientific reports. 2019 ; Vol. 9, No. 1.
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