Quantitative models of photoreceptor metabolisms: implications for rod outer segment length, retinal glycolysis and...

The outer retina exhibits several distinctive physiological features, including continuous turnover of rod photoreceptor outer segments (OS), a strong reliance on aerobic glycolysis despite oxygen availability, and an unusually high rate of choroidal blood flow. The mechanistic links between these phenomena remain incompletely understood. Here, we present a quantitative reaction-diffusion model of energy metabolism in rod photoreceptors that connects metabolic supply and demand to OS length and daily shedding. Because rod OS lack mitochondria, ATP and glycolytic intermediates must be supplied by diffusion from the inner segment, where oxidative phosphorylation and the initial steps of glycolysis occur. We model the diffusion and consumption of ATP and fructose-1,6-bisphosphate along the OS and show that diffusion-limited energy supply constrains OS length. Using literature-derived parameters, the model accurately predicts observed OS lengths in mammals (∼28µm) and amphibians (∼50µm), explains diurnal variations in OS length and tip shedding at light onset, and provides a unified explanation for the coexistence of high glycolytic flux, low oxygen extraction, and high choroidal blood flow in the outer retina. The model generates experimentally testable predictions regarding metabolite gradients along the OS and offers a general framework for understanding how metabolic constraints shape cellular morphology and tissue-level physiology.