Short-Wavelength Light Sensitivity of Circadian, Pupillary, and Visual Awareness in Humans Lacking an Outer Retina

Farhan H Zaidi,Joseph T Hull,Stuart N Peirson,Katharina Wulff,Daniel Aeschbach,Joshua J Gooley,George C Brainard,Kevin Gregory-Evans,Joseph F Rizzo,Charles A Czeisler,Russell G Foster,Merrick J Moseley,Steven W Lockley

doi:10.1016/j.cub.2007.11.034

Abstract

SummaryAs the ear has dual functions for audition and balance, the eye has a dual role in detecting light for a wide range of behavioral and physiological functions separate from sight [1–11]. These responses are driven primarily by stimulation of photosensitive retinal ganglion cells (pRGCs) that are most sensitive to short-wavelength (∼480 nm) blue light and remain functional in the absence of rods and cones [8–10]. We examined the spectral sensitivity of non-image-forming responses in two profoundly blind subjects lacking functional rods and cones (one male, 56 yr old; one female, 87 yr old). In the male subject, we found that short-wavelength light preferentially suppressed melatonin, reset the circadian pacemaker, and directly enhanced alertness compared to 555 nm exposure, which is the peak sensitivity of the photopic visual system. In an action spectrum for pupillary constriction, the female subject exhibited a peak spectral sensitivity (λmax) of 480 nm, matching that of the pRGCs but not that of the rods and cones. This subject was also able to correctly report a threshold short-wavelength stimulus (∼480 nm) but not other wavelengths. Collectively these data show that pRGCs contribute to both circadian physiology and rudimentary visual awareness in humans and challenge the assumption that rod- and cone-based photoreception mediate all “visual” responses to light.

Highlights

Two blind subjects without light perception were studied in parallel experiments
Fundus photography and ocular coherence tomography failed to identify an outer retina in the female subject, and electroretinography demonstrated no detectable rod or cone function (Figure 1)
In order to compare the relative contribution of the photosensitive retinal ganglion cells and classical photoreceptors, we chose two light sources that would differentially stimulate these systems: a monochromatic “blue” light source with a peak emission at 460 nm and close to the λmax of human pRGCs (∼480 nm) [11, 19], and a monochromatic light source with a λmax at 555 nm corresponding to the peak of human photopic vision. Given that this subject exhibited a 24-hr sleep-wake pattern and an entrained aMT6s rhythm, we predicted that the pRGC/melanopsindriven system would be intact and that the short-wavelength stimulus would elicit full circadian, neuroendocrine, and neurobehavioral responses, whereas the lack of classical photoreception would preclude any response to mid-wavelength 555 nm light

Summary

Introduction

Given that this subject exhibited a 24-hr sleep-wake pattern and an entrained aMT6s rhythm, we predicted that the pRGC/melanopsindriven system would be intact and that the short-wavelength stimulus would elicit full circadian, neuroendocrine, and neurobehavioral responses, whereas the lack of classical photoreception would preclude any response to mid-wavelength 555 nm light.

Objectives

Results

Conclusion