Plenary talk

Speaker: Erika Tatiana Camacho (University of Texas at San Antonio)

Location and Time: SAS 121, Saturday, 3:00–4:00 PM

Title: Analyzing Mathematical Models of Photoreceptor Metabolism

Abstract: Cell degeneration, including that resulting in retinal diseases such as retinitis pigmentosa and AMD, is linked to metabolic issues. In the retina, photoreceptor degeneration can result in disturbances of glucose levels and metabolic processes. To identify the key mechanisms in metabolism that may be culprits of this degeneration, we develop and investigate mathematical models of the metabolic pathway of aerobic glycolysis in a healthy cone photoreceptor.

In one case, we mathematically model cone molecular and photoreceptor cellular interactions and identify three key processes. 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 rod-derived cone viability factor (RdCVF) signal to compensate. In the other case, we model a single cone cell and focus on the interplay of external glucose, the efficiency of glucose transporter 1 (GLUT1), lipid utilization for photoreceptor outer segments (POS) renewal, and oxidation of fatty acids.

We perform numerical simulations, use available metabolic data to estimate parameters and fit the models to this data.  We conduct uncertainty and sensitivity analysis to identify the processes that have the largest impact on each system. The ability of these mechanisms to affect key metabolites’ levels, as revealed in our analyses, signifies the importance of inter-dependent and inter-connected feedback processes modulated by and affecting cone’s metabolism. We show that joint variations in these processes affect the cone’s metabolic vitality and its capability to adapt under glucose-deficient conditions. Our analysis also reveals that when glucose is scarce cone viability requires supporting anabolic processes to create lipids necessary for cell maintenance and repair.  The results reveal a critical temporal window where there would be more flexibility for interventions to rescue a cone cell from the detrimental consequences of glucose shortage.