Parkinson’s disease (PD) is characterised by non-motor symptoms including sleep and circadian disruption. Melanopsin-expressing intrinsically photosensitive Retinal Ganglion Cells (ipRGC) transmit light signals to brain areas controlling circadian rhythms and the pupil light reflex. To determine if non-motor symptoms observed in PD are linked to ipRGC dysfunction, we evaluated melanopsin and rod/cone contributions to the pupil response in medicated participants with PD (n = 17) and controls (n = 12). Autonomic tone was evaluated by measuring pupillary unrest in darkness. In the PD group, there is evidence for an attenuated post-illumination pupil response (PIPR) amplitude and reduced pupil constriction amplitude, and PIPR amplitudes did not correlate with measures of sleep quality, retinal nerve fibre layer thickness, disease severity, or medication dosage. Both groups exhibited similar pupillary unrest. We show that melanopsin- and the rod/cone-photoreceptor contributions to the pupil control pathway are impaired in people with early-stage PD who have no clinically observable ophthalmic abnormalities. Given that ipRGCs project to brain targets involved in arousal, sleep and circadian rhythms, ipRGC dysfunction may underpin some of the non-motor symptoms observed in PD.
Beyond visual function, specialized light-sensitive retinal circuits involving the photopigment melanopsin drive critical aspects of human physiology and behavior, including sleep–wake rhythms, hormone production, mood, and cognition. Fundamental discoveries of visual neurobiology dating back to the 1990s have given rise to strong interest from the lighting industry in optimizing lighting to benefit health. Consequently, evidence-based recommendations, regulations, and policies need to translate current knowledge of neurobiology into practice. Here, reviewing recent advances in understanding of NIF circuits in humans leads to proposed strategies to optimize electric lighting. Highlighted knowledge gaps must be addressed urgently, as well as the challenge of developing personalized, adaptive NIF lighting interventions accounting for complex individual differences in physiology, behavior, and environment. Finally, lighting equity issues appear in the context of marginalized groups, who have traditionally been underserved in research on both fundamental visual processes and applied lighting. Biologically optimal light is a fundamental environmental right.
1 October 2016 in Investigative Ophthalmology & Visual Science
Purpose: We determine the effect of short-term light adaptation on the pupil light reflex and the melanopsin mediated post-illumination pupil response (PIPR). Inner and outer retinal photoreceptor contributions to the dark-adapted pupil response were estimated. Methods: In Experiment A, light adaptation was studied using short wavelength lights ranging from subthreshold to suprathreshold irradiances for melanopsin signaling that were presented before (5–60 seconds) and after (30 seconds) a melanopsin-exciting stimulus pulse. We quantified the pupil constriction and the poststimulus response amplitudes during dark (PIPR) and light (poststimulus pupil response, PSPR) adaptation. In Experiment B, colored prestimulus adapting lights were univariant for melanopsin or rod excitation. Results: Increasing the prestimulus duration and irradiance of adapting lights increased the pupil constriction amplitude when normalized to the dark-adapted baseline but reduced its amplitude when normalized to the light-adapted baseline. Light adaptation at irradiances suprathreshold for melanopsin activation increased the PIPR amplitude, with larger changes at longer adaptation durations, whereas the PSPR amplitude became more attenuated with increasing irradiances, independent of duration. Rod versus melanospin univariant adaptation did not alter the constriction amplitude but increased the PIPR amplitude in the rod condition. Correlations between millimeter pupil constriction and PIPR amplitudes were eliminated when normalized to the baseline diameter. Conclusions: The findings have implications for standardizing light adaptation paradigms and the choice of pupil metrics in both laboratory and clinical settings. Light and dark adaptation have opposite effects on the pupil metrics, which should be normalized to baseline to minimize significant correlations between constriction and PIPR amplitudes.
Intrinsically photosensitive retinal ganglion cells (ipRGCs) regulate pupil size by integrating extrinsic rod and cone signals with intrinsic melanopsin-mediated phototransduction. Light adapted pupil diameter is determined by the corneal flux density (CFD), and for central visual field stimulation the melanopsin-mediated post-illumination pupil response (PIPR) follows this same CFD relationship. Rods, cones, and ipRGCs vary in size, density, and distribution across the retina, but how these differences affect the amplitude and timing of the extrinsic and intrinsic pupil light reflex in the central and peripheral retina is unknown. We determined the relationship between stimulus area and photon flux with stimuli constant for CFD, irradiance, or area at central (0°) and peripheral (20°) eccentricities with high and low melanopsin excitation. We show that the pupil constriction amplitude was similar at both eccentricities and the time to minimum diameter increased as melanopsin excitation increased. In contrast, the peripheral PIPR follows a CFD relationship but with lower amplitude compared with that at the fovea. This indicates differences in the spatial and temporal characteristics of extrinsic and intrinsic ipRGC inputs to the pupil control pathway for the central and peripheral retina. The eccentricity-dependent change in PIPR amplitude may be analogous to the hill of vision observed in visual perimetry; such knowledge is an important precursor to the development of pupil perimetry paradigms to measure the PIPR in select regions of the visual field.
19 December 2013 in Journal of the Optical Society of America A
We studied the effect of rod–cone interactions on mesopic visual reaction time (RT). Rod and cone photoreceptor excitations were independently controlled using a four-primary photostimulator. It was observed that (1) lateral rod–cone interactions increase the cone-mediated RTs; (2) the rod–cone interactions are strongest when rod sensitivity is maximal in a dark surround, but weaker with increased rod activity in a light surround; and (3) the presence of a dark surround nonselectively increased the mean and variability of chromatic (, S-cone) and luminance () RTs independent of the level of rod activity. The results demonstrate that lateral rod–cone interactions must be considered when deriving mesopic luminous efficiency using RT.