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Description
Photoreceptors are cells in the retina that convert light to chemical signals. To offset the extreme optical and metabolic demands, and thereby prevent the toxic effects of accumulated photo-oxidative products, photoreceptors undergo renewal and periodic shedding of their outer segment (OS) discs. The OS are a substructure that carries the light sensitive molecule, opsin. People afflicted with diseases such as Retinitis Pigmentosa (RP) and Age-Related Macular Degeneration (AMD) experience a decline in vision due to photoreceptor degeneration. When photoreceptors degenerate, the shedding and renewal is interrupted eventually resulting in the disappearance of the OS and followed by the death of the cells. Currently there is no cure for diseases linked to photoreceptor degeneration. Motivated by photoreceptor degeneration, in particular RP which is typically categorized by a loss of rods (carriers of the faulty gene) followed by the loss of healthy cones, we focus our efforts on understanding the mechanisms necessary for cone survival. In an effort to begin to unravel the key process in photoreceptor functionality and vitality, this work considers key cone metabolic processes in a healthy retina. Recently it was discovered that the protein Rod-derived Cone Viability Factor (RdCVF) preserves the cones by stimulating aerobic glycolysis and accelerating the uptake of glucose needed for OS renewal and vitality in cones. Utilizing this understanding we developed a nonlinear system of ordinary differential equations to mathematically model molecular and cellular level interactions. We qualitatively validate the model and use uncertainty and sensitivity analysis to identify the processes and mechanisms that are crucial for cones vitality and functionality. Our result indicate that when all processes are functioning properly changes in key parameters at the subcellular level as well as the cellular level can significantly affect the cone population. Our analysis additionally examined the role of inefficient glucose use by the cones as well as restricted availability of RdCVF has on the overall cone populations. These results can lead to important insight into the design of new experiments such as the particular experiments that give the most valuable information, and at what time point a particular process (defined by a parameter) should be altered to increase the vitality of the cones.
