July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Mathematically Assessing the Contributions of Key Processes in Cone Aerobic Glycolysis
Author Affiliations & Notes
  • Danielle Brager
    School of Mathematical and Statistical Sciences, Arizona State University, Tempe, Arizona, United States
  • Erika Tatiana Camacho
    School of Mathematical & Natural Sciences, Arizona State University, Glendale, Arizona, United States
  • Ghizlane Elachouri
    Genetics, Institut de la Vision, Paris, France
  • Tatyana Korneyeva
    School of Mathematical & Natural Sciences, Arizona State University, Glendale, Arizona, United States
  • Geraldine Millet-Puel
    Genetics, Institut de la Vision, Paris, France
  • Jose Alain Sahel
    Genetics, Institut de la Vision, Paris, France
  • Thierry D Leveillard
    Genetics, Institut de la Vision, Paris, France
  • Footnotes
    Commercial Relationships   Danielle Brager, None; Erika Camacho, None; Ghizlane Elachouri, None; Tatyana Korneyeva, None; Geraldine Millet-Puel, None; Jose Sahel, None; Thierry Leveillard, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 569. doi:
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      Danielle Brager, Erika Tatiana Camacho, Ghizlane Elachouri, Tatyana Korneyeva, Geraldine Millet-Puel, Jose Alain Sahel, Thierry D Leveillard; Mathematically Assessing the Contributions of Key Processes in Cone Aerobic Glycolysis . Invest. Ophthalmol. Vis. Sci. 2019;60(9):569.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : The degenerative disease Retinitis Pigmentosa (RP) is typically categorized by loss of
night vision due to rod degeneration and eventually progressing to daylight-blindness and
cone death. The cones rely on aerobic glycolysis to supply the metabolites necessary for renewal and maintenance of the photoreceptors. In this work, we mathematically investigate the biochemical processes in the retina triggered by glucose catabolism in cones.

Methods : Applying Latin Hypercube Sampling and global sensitivity analysis to a mathematical model of cone aerobic glycolysis, we assess the reliance of cones on rods via the Rod-derived cone viability factor (RdCVF) and investigate which processes contribute the most to the renewal of the cone photoreceptors. Utilizing these mathematical approaches required parameter space restrictions and monotonicity of the cones as a function of each parameter. The Partial Rank Correlation Coefficient and p-value were used as criteria to determine which parameters were statistically significant.

Results : When considering low levels of glucose or RdCVF our analysis identified three key processes for cone renewal and maintenance: metabolism of fructose-1,6-bisphosphate, production of glycerol-3-phosphate, and the competition that rods exert on cone resources. Uncertainty and sensitivity analysis also revealed the processes with the largest effect on the system at various timeframes.

Conclusions : Our findings demonstrate the importance of the partition of the carbon flux between glycolysis and the pentose phosphate pathway or the Kennedy pathway. Additionally, the competition from the rods for glucose may provide an explanation of why the rods provide the RdCVF signal to compensate.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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