The influence of intrinsically-photosensitive retinal ganglion cells on the spectral sensitivity and response dynamics of the human pupillary light reflex

Abstract

Historically, it was assumed that the light-evoked neural signals driving the human pupillary light reflex (PLR) originated exclusively from rod and cone photoreceptors. However, a novel melanopsin-containing photoreceptive cell class has recently been discovered in the mammalian retina. These intrinsically photosensitive retinal ganglion cells (ipRGCs) project to the pretectum, the retinorecipient area of the brain responsible for the PLR. This study was therefore designed to examine the relative contribution of rod, cone and the melanopsin photoresponses of ipRGCs to the human PLR. We establish that the melanopsin photoresponse of ipRGCs contributes significantly to the maintenance of half maximal pupilloconstriction in response to light stimuli of 30 seconds or longer, even at low photopic irradiances. Furthermore, we show that the melanopsin photoresponse contributes significantly to three- quarter maximal pupilloconstriction in response to light stimuli as short as 2 seconds. We also demonstrate that cone photoresponses driving pupilloconstriction adapt considerably and contribute little after 30 seconds, but rod photoresponses adapt less and contribute significantly to the maintenance of pupilloconstriction in response to steady-state light stimuli at irradiance levels which are below the threshold of the melanopsin photoresponse.

Contribution of human melanopsin retinal ganglion cells to steady-state pupil responses

“…Alpern & Ohba 1972;Hansen & Fulton 1986;McDougal & Gamlin 2010). Further, McDougal and Gamlin have recently shown that mRGCs and rods contribute significantly to pupil constriction for test stimuli with duration of 100 s, whereas cones contribute little (McDougal & Gamlin 2010), suggesting that rod activity can influence the pupil even when using a steady background. We used bright stimuli with approximately 3640 scotopic trolands for the control stimulus and the lowest retinal illuminance used was approximately 1710 scotopic trolands throughout to eliminate the intrusion of rods.…”

143 A Unified Formula For Light-adapted Pupil Size

“…These cells express the photopigment melanopsin, with an action spectrum peaking at about 483 nm. These cells have been shown to exert significant control over the steady state pupil response in both macaque and human (Gamlin et al, 2007;McDougal & Gamlin, 2010). Thus while we have considered photopic luminance as the controlling variable, the action spectrum of the actual controlling quantity is likely to be a more complex mixture of rod, cone, and ipRGC sensitivities.…”

Image and Non-Image Forming Melanopsin Function in Age-Related Macular Degeneration

“…The newly defined PAP (phase amplitude percentage) metric , calculated as ( 638 −464 638 ) 100, used the phasic response during light stimulation to measure inner and outer retinal interactions. As ipRGCs contribute to maintaining pupil constriction during stimulus presentation, the peak-to-trough amplitude for the short wavelength sinusoid stimulus is lower than that of the long wavelength stimulus under normal conditions Güler et al 2008;McDougal & Gamlin 2010). In retinal disease conditions, ipRGC loss or dysfunction would reduce pupil constriction during light stimulation, resulting in a similar peak-to-trough amplitude for both high and low melanopsin excitation stimuli (i.e.…”

“…The inner retina includes the conventional ganglion cells (RGC) and melanopsin expressing ganglion cells (M 1 and M 2 in humans and primates) with dendrites that stratify in the inner plexiform layer (IPL) and which project to various centres in the brain that regulate image-forming functions (vision; green line) and non-imageforming functions (sleep, mood and pupil; brown lines). With projections to the olivary pretectal nucleus (OPN) that mediate the pupil light reflex (PLR) (Gamlin et al 2007;Lucas, Douglas & Foster 2001a;Markwell, Feigl & Zele 2010;McDougal & Gamlin 2010), ipRGC function can be measured in vivo.…”

“…The Pupil Light Reflex (PLR) provides a rapid, objective, non-invasive measure of both inner (ipRGC) and outer (rod and cone) retinal function (Adhikari et al 2015b;Herbst, Sander, Milea, Lund-Andersen & Kawasaki 2011;Kankipati et al 2010;Kardon et al 2009;Markwell et al 2010;McDougal & Gamlin 2010;Park et al 2011). Following onset of an incremental light pulse, the initial PLR is mediated by the outer retina (Güler et al 2008;McDougal & Gamlin 2010) with increasing melanopsin input with longer stimulus durations (McDougal & Gamlin 2010), while ipRGCs control the Post-Illumination Pupil Response (PIPR), the sustained pupil constriction after light offset (Adhikari et al 2015b;Gamlin et al 2007). Recently it was demonstrated that for sinusoidal lights with high melanopsin excitation, the peak-to-trough amplitude of the phasic PLR during flicker stimulation was suppressed compared to lights with low melanopsin excitation Joyce et al 2015).…”