DECODING LIGHT-DEPENDENT DOPAMINE DYNAMICS IN THE RETINA

Dopamine is the most abundant catecholamine in the vertebrate retina, where it is released by dopaminergic amacrine cells. It plays a central role in light–dark adaptation and circadian regulation, and alterations in retinal dopamine signaling have been linked to visual disorders such as myopia. Illumination levels strongly influence dopamine synthesis and release and follow a circadian pattern; however, the precise light conditions governing its release remain poorly understood, largely due to the difficulty of directly measuring dopamine dynamics. Recent advances in genetically encoded dopamine sensors now enable real-time monitoring of dopamine signaling in vivo.

In this study, we investigated retinal dopamine dynamics under different light conditions using the genetically encoded sensor GRABDA, delivered via intravitreal injection to target retinal neurons. Consistent with previous findings, dopamine release was reliably evoked by prolonged light stimulation (≥40 s). Responses were predominantly sustained, with the lowest effective light intensity eliciting a detectable response at 2.68 µW/cm² (R* = 1.07 × 10⁴ isomerizations/ph/s). Notably, dopamine responses persisted following pharmacological blockade of photoreceptor transmission, suggesting a contribution of melanopsin-expressing ganglion cells to dopamine release. In addition, visual stimuli designed to manipulate contrast revealed that dopamine signaling can be modulated by contrast changes.

Together, these results demonstrate robust expression of GRABDA in the retina and establish its utility for real-time measurement of light-evoked dopamine release. Our findings indicate that retinal dopamine release is primarily driven by illumination levels and is likely shaped by contrast-dependent visual processing.