School of Mathematical and Statistical Sciences, Arizona State University, Tempe, AZ, United States.
School of Mathematical & Natural Sciences, Arizona State University, Glendale, AZ 85306, United States.
J Theor Biol. 2021 Jul 7;520:110642. doi: 10.1016/j.jtbi.2021.110642. Epub 2021 Feb 23.
Recent experimental and mathematical work has shown the interdependence of the rod and cone photoreceptors with the retinal pigment epithelium in maintaining sight. Accelerated intake of glucose into the cones via the theoredoxin-like rod-derived cone viability factor (RdCVF) is needed as aerobic glycolysis is the primary source of energy production. Reactive oxidative species (ROS) result from the rod and cone metabolism and recent experimental work has shown that the long form of RdCVF (RdCVFL) helps mitigate the negative effects of ROS. In this work we investigate the role of RdCVFL in maintaining the health of the photoreceptors. The results of our mathematical model show the necessity of RdCVFL and also demonstrate additional stable modes that are present in this system. The sensitivity analysis shows the importance of glucose uptake, nutrient levels, and ROS mitigation in maintaining rod and cone health in light-damaged mouse models. Together, these suggests areas on which to focus treatment in order to prolong the photoreceptors, especially in situations where ROS is a contributing factor to their death such as retinitis pigmentosa.
最近的实验和数学工作表明，视杆和视锥光感受器与视网膜色素上皮在维持视力方面是相互依存的。需要通过类硫氧还蛋白样视杆衍生的锥生存因子（RdCVF）加速将葡萄糖摄入锥体内，因为有氧糖酵解是能量产生的主要来源。活性氧（ROS）是由视杆和视锥代谢产生的，最近的实验工作表明，RdCVF 的长链形式（RdCVFL）有助于减轻 ROS 的负面影响。在这项工作中，我们研究了 RdCVFL 在维持光感受器健康中的作用。我们的数学模型结果表明了 RdCVFL 的必要性，并展示了该系统中存在的其他稳定模式。敏感性分析表明，在光损伤小鼠模型中，维持视杆和视锥健康需要关注葡萄糖摄取、营养水平和 ROS 缓解。总的来说，这些研究表明了需要关注的治疗领域，以延长光感受器的寿命，特别是在 ROS 是导致其死亡的因素的情况下，如色素性视网膜炎。
