Differential maturation of mRGC pupillary constriction and circadian rhythmicity in typically developing human infants

Intrinsically light sensitive retinal ganglion cells through melanopsin photoreception (mRGCs) are important for fundamental regulatory brain processes such as circadian rhythms, mood, acute sleep, and pupillary constriction. While previous research in animal models indicates temporal differences in maturation of mRGC mediated projections, corresponding developmental patterns have not been studied in human infants. To elucidate the roles of mRGCs in early development of regulation of pupillary constriction and sleep/wake patterns, we here explore the maturation of mRGC mediated photoentrainment in human infants aged 1 to 12 months, using non-invasive eye tracking pupillometry and sleep diaries. Although the mRGCs relay rod/cone activation in a range of light intensities, it is possible to separate rod/cone/mRGC activation due to the photoreceptors' color sensitivity and temporal responsiveness. We therefore used sustained red and blue light stimulation after partial dark adaptation to characterize developmental changes in wavelength-dependent mRGC-relayed pupillary responses. Infants' pupil responses indicate a prolonged post-natal mRGC maturation to the shell of the olivary pretectal nucleus during the first year. This response was separate from infants' sleep/wake patterns, which parallels findings from cellular research on murines: the mRGCs have separate pathways for photoentrainment of pupillary constriction and sleep/wake patterns, which develop with different temporal dynamics. Together, these findings provide the first characterization of developmental changes in mRGC-relayed pupillary responses in human infants, and an initial step towards bridging human mRGC network development with murine and human adult mRGC research.