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Background  In the human retina, the contribution of intrinsically photosensitive retinal ganglion cells (ipRGCs) to the regulation of the pupillary response remains poorly understood. The objective of the current study was to determine the response dynamics of the pupillary light reflex to short, successive pulses of light. In order to better assess the roles of ipRGCs and cones, we used pulses of blue and green light.    Methods  Each participant was exposed to 1-ms blue (466 nm) and/or green (527 nm) light pulses simultaneously or separately, with inter-stimulus intervals (ISIs) of 0, 250, 500, 750, or 1000 ms. Pupil diameter was measured using an infrared camera system.    Results  We found that human pupillary light responses during simultaneous irradiation or successive irradiation with ISIs ≤ 250 ms were equivalent, though successive irradiation of blue- and green-pulsed light with ISIs ≥ 500 ms induced markedly increased pupillary constriction.    Conclusions  We propose that this result may be related to cell hyperpolarization that occurs in the retina just after the first light stimulus is turned off, with the threshold for this effect being between 250 and 500 ms in the human retina.

Human pupillary light reflex during successive irradiation with 1-ms blue- and green-pulsed light