Camacho Erika T, Léveillard Thierry, Sahel José-Alain, Wirkus Stephen
School of Mathematical and Natural Sciences, Arizona State University, Glendale, AZ, 85306, USA.
INSERM, U968, 75012, Paris, France.
Bull Math Biol. 2016 Jul;78(7):1394-409. doi: 10.1007/s11538-016-0185-x. Epub 2016 Jul 21.
Understanding the essential components and processes for coexistence of rods and cones is at the forefront of retinal research. The recent discovery on RdCVF's mechanism and mode of action for enhancing cone survival brings us a step closer to unraveling key questions of coexistence and codependence of these neurons. In this work, we build from ecological and enzyme kinetic work on functional response kinetics and present a mathematical model that allows us to investigate the role of RdCVF and its contribution to glucose intake. Our model results and analysis predict a dual role of RdCVF for enhancing and repressing the healthy coexistence of the rods and cones. Our results show that maintaining RdCVF above a threshold value allows for coexistence. However, a significant increase above this value threatens the existence of rods as the cones become extremely efficient at uptaking glucose and begin to take most of it for themselves. We investigate the role of natural glucose intake and that due to RdCVF in both high and low nutrient levels. Our analysis reveals that under low nutrient levels coexistence is not possible regardless of the amount of RdCVF present. With high nutrient levels coexistence can be achieved with a relative small increase in glucose uptake. By understanding the contributions of rods to cones survival via RdCVF in a non-diseased retina, we hope to shed light on degenerative diseases such as retinitis pigmentosa.
了解视杆细胞和视锥细胞共存的基本组成部分和过程是视网膜研究的前沿课题。最近关于RdCVF增强视锥细胞存活的机制和作用方式的发现,使我们在解开这些神经元共存和相互依赖的关键问题上又迈进了一步。在这项工作中,我们基于功能反应动力学的生态学和酶动力学研究成果,构建了一个数学模型,该模型使我们能够研究RdCVF的作用及其对葡萄糖摄取的贡献。我们的模型结果和分析预测了RdCVF在增强和抑制视杆细胞与视锥细胞健康共存方面的双重作用。我们的结果表明,将RdCVF维持在阈值以上可实现共存。然而,当该值大幅增加时,会威胁到视杆细胞的生存,因为视锥细胞摄取葡萄糖的效率变得极高,并开始将大部分葡萄糖据为己有。我们研究了在高营养水平和低营养水平下天然葡萄糖摄取以及由于RdCVF导致的葡萄糖摄取的作用。我们的分析表明,在低营养水平下,无论存在多少RdCVF,都不可能实现共存。在高营养水平下,通过相对少量增加葡萄糖摄取就可以实现共存。通过了解在非患病视网膜中视杆细胞通过RdCVF对视锥细胞存活的贡献,我们希望能为诸如视网膜色素变性等退行性疾病提供线索。