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Dingcai Cao, Pablo Alejandro Barrionuevo; Melanopsin-mediated light adaptation measured from human pupil flicker responses. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4016.
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© ARVO (1962-2015); The Authors (2016-present)
Intrinsically photosensitive retinal ganglion cells (ipRGCs) can be activated by intrinsic melanopsin phototransduction as well as by extrinsic inputs from rods and cones. Studying melanopsin-based functions is challenging in humans, due to the difficulty in isolating melanopsin activation from rod and cone inputs. Here we introduced a five-primary photostimulator that can control the excitations of rods, S-, M-, L-cones and melanopsin at a constant light level to allow for assessment of melanopsin-, rod- or cone-mediated light adaptation.
The photostimulator included a bundle of five optic fibers to transmit the lights from the five bright LEDs through a homogenizer and diffuser to achieve a homogeneous field. The lights from 5 LEDs (dominant wavelengths of 456 nm, 488 nm, 540 nm, 592 nm, and 632 nm) were controlled by a laboratory-created board using Pulse Width Modulation dimming. Using a silent substitution method, the photostimulator could generate photoreceptor-isolating stimuli that modulated the rod excitations alone (R), cone excitations alone (S-, M- or L), melanopsin excitation alone (I), or any combinations of the photoreceptor signals. We measured human pupil responses with the L, M, S, R, I, L+M, L+M+S, L+M+S+R, L+M+S+R+I modulations (16% contrast, 1 Hz, mean retinal illuminance of 2 Td-20000 Td in a one log unit step), using an EyeLink II Eyetracker (SR Research). For each condition, pupillary response amplitude and phase were derived from Fourier analysis.
For all modulation types, the pupil response amplitudes increased with increasing light levels, although the pupil responses were not measurable for the melanopsin modulation at 2 Td due to below melanopsin activation threshold, for the rod modulation at 2000 and 20000 Td due to saturation, and for the S- modulation at 2 and 20 Td due to low contrast sensitivity. The melanopsin-mediated pupil responses had similar phases to rods, L, M, L+M stimuli but was out of phase with the S-cone-mediated response. While the phases with the rod or cone-mediated responses were relatively stable over 2 Td -20000 Td, the phase of melanopsin-mediated responses increases with increasing light levels, suggesting speeding up of the melanopsin phototransduction.
Melanopsin displays a unique light adaptation characteristic compared with rod- and cone-mediated light adaptation in pupil flicker responses.
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