Measuring and using light in the melanopsin age

Abstract

Light is a potent stimulus for regulating circadian, hormonal, and behavioral systems. In addition, light therapy is effective for certain affective disorders, sleep problems, and circadian rhythm disruption. These biological and behavioral effects of light are influenced by a distinct photoreceptor in the eye, melanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs), in addition to conventional rods and cones. We summarize the neurophysiology of this newly described sensory pathway and consider implications for the measurement, production, and application of light. A new light-measurement strategy taking account of the complex photoreceptive inputs to these non-visual responses is proposed for use by researchers, and simple suggestions for artificial/architectural lighting are provided for regulatory authorities, lighting manufacturers, designers, and engineers.

Figure 1. All retinal photoreceptor classes are upstream of circadian, neuroendocrine and neurobehavioral responses to light

A. Schematic of the relevant retinal circuitry in humans. Non-image-forming responses originate in the retina and have been attributed to a particular class of retinal ganglion cell (ipRGC). ipRGCs are directly photosensitive owing to expression of melanopsin, which allows them to respond to light even when isolated from the rest of the retina. In situ they are connected to the outer retinal rod and cone photoreceptors via the conventional retinal circuitry. The details of their intraretinal connections are incompletely understood and probably vary between different subtypes. Shown here are major connections with on cone bipolar cells (on CBCs) connecting them to cone and, via amacrine cells (AII) and rod bipolar cells (RBC), rod photoreceptors. As a consequence, the firing pattern of ipRGCs can be influenced both by intrinsic melanopsin photoreception, and extrinsic signals originating in rods and each of the spectrally distinct cone classes (shown in red, green and blue). B. This feature is conceptualized in much simplified form, as a number of photoreceptive mechanisms (depicted as R for rod opsin; M for melanopsin; SC for S cone opsin; MC for M cone opsin; and LC for L-cone opsin), each of which absorbs light according to its own spectral sensitivity profile (shown in cartoon form as plots of log sensitivity against wavelength from 400 to 700 nm) to generate a distinct measure of illuminance. These five input signals are then combined by the retinal wiring, and within the ipRGC itself, to produce an integrated signal that is sent to non-image-forming centers in the brain. As each of the five representations of weighted irradiance is produced by a photopigment with its own spectral sensitivity profile, their relative significance for the integrated output defines the wavelength dependence of this signal, and hence of downstream responses.

Figure 2. Spectral sensitivity of half-maximal pupillary constriction in humans

(A). The pupillary light reflex response is composed of several different temporal components. At light onset, the pupil shows a rapid, transient constriction during the first 1000 ms of light exposure. This is followed by redilation to a tonic or sustained pupil diameter that stabilizes to a steady state constriction (photoequilibrium) even during prolonged constant illumination. When the light is turned off, there is a slow, delayed redilation of the pupil back to the resting (dark-adapted) state that is melanopsin-driven. Graph adapted from [76]. B. Mean spectral sensitivity is depicted as the retinal irradiance (log quanta/cm²/s) required to elicit a criterion pupil response (half maximal constriction) at nine wavelengths for three different stimulus durations of 1, 10, and 100 s (corresponding to the positions of blue, red, and green arrows in A). The smooth curve through the data points represents the optimal fit to the data using a mathematical combination of rod, cone, and melanopsin spectral sensitivities. As the stimulus duration increases, the sensitivity of the response gradually decreases by more than one log unit and is shifted towards shorter wavelength, from 510 nm at 1 s, to 500 nm at 10 s, and 480 nm at 100 s. Graph derived from data in [77]. (C) Representative traces for pupillary constriction in a sighted participant (gray) and in a blind individual without rod and cone function (black). Pupillary constriction to 480 nm was sluggish and lacks the transient response after light onset in the blind individual, whereas the sustained steady state pupillary light reflex (PLR) and the persistent response when the light is turned off are conserved. Graph reproduced, with permission, from [29].