Visualizing Extracellular Dopamine Dynamics in the Retina Reveals a Biphasic Reduction During Initial Myopia Development.

Abstract

PURPOSE: Extracellular dopamine (DA) is the immediate source of biologically active dopaminergic signaling in the retina, yet conventional bulk assay methods measure only total DA content. We aimed to develop a procedure to monitor changes in retinal extracellular DA concentration and characterize its spatiotemporally dependent changes during the initial stages of myopia development. METHODS: Using mice, we employed genetically encoded DA sensors and developed an effective delivery strategy for inducing efficient transduction in many types of retinal cells. We confirmed normal spatiotemporal resolution, sensitivity, specificity, and safety after delivery and applied this system to quantify extracellular DA levels in the central and peripheral retina after 2, 3, 6, 9, and 12 hours of form deprivation. RESULTS: We established a reliable strategy for direct monitoring of retinal extracellular DA dynamics. The DA sensors exhibit high sensitivity, selectivity, and a suitable dynamic range for measuring physiologically relevant concentrations of extracellular DA. Using this technology, we identified a significant reduction in extracellular DA levels during myopia development. Crucially, this reduction followed a biphasic temporal pattern within the first 12 hours of form deprivation, with distinct phases of decreased concentration at 3 and 12 hours in the central retina and at 3 and 9 hours in the peripheral retina. CONCLUSIONS: Our study represents a key methodological advance, providing for visualizing and quantifying extracellular DA dynamics in the retina. The discovery of a biphasic reduction in DA concentration suggests that dopaminergic deficiency during initial myopia development involves complex, active regulatory mechanisms rather than a simple monotonic decline.