Why do melanopsin-containing retinal ganglion cells have the greatest sensitivity to blue light?

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Pupils are constantly in motion; even when they are steady, pupillary fluctuations (hippus) are detectable (Loewenfeld 1999). Two involuntary fluctuations are pupillary unrest, visible to the unaided eye, and pupillary oscillation, detectable with special equipment. Pupillary oscillation originates in the central nervous system (Wilhelm et al. 2014). Pupillary unrest delineates natural fluctuations in the eye, the significance of which remains unknown. A novel photoreceptor containing an intrinsically photosensitive visual pigment called melanopsin was discovered in retinal ganglion cells (mRGCs). mRGCs are independent conventional photoreceptors essential in ‘non-image forming vision’ by circadian entrainment, melatonin suppression and pupil size regulation. mRGC-mediated pupil response is selectively sensitive to short-wavelength light (peaks, 460–480 nm) and shows constant pupil constricting reactions even after discontinued blue light stimulus (sustained pupil constriction) (Kawasaki & Kardon 2007). Most people would say that the most common blue light is the colour of the sky. The atmosphere contains air molecules and other microscopic particles that scatter the sun's rays, so that only shorter wavelengths, especially blue, are visualized. The wavelength components of daytime and their spectral irradiance under natural light conditions remain unknown. The association between pupil size and daily natural light is unclear. We hypothesized that pupillary unrest, especially the sustained phase of pupillary change, is associated with the characteristics of mRGCs. We examined 10 eyes of healthy subjects (five men and five women) ranging in age from 21 to 32 years. Study protocol was approved by our Institutional Ethics Committee. This study followed the tenets of the Declaration of Helsinki for research involving human subjects, and informed consent was obtained. All examinations were conducted by an experienced examiner (KA). A spectral radiometer MS-720 (EKO Instruments, Tokyo, Japan) was used to measure the natural light wavelength components and the spectral radiant intensity between 07:00 and 19:00 at 3-hr intervals in a room with natural light at 35°, 32′ latitude and 139°, 23′ longitude. A goggle-type infrared pupillometer (Hamamatsu Photonics, Hamamatsu, Japan) was used to measure pupil size changes under natural light conditions. Subjects looked at a screen, 60 cm distant, and were instructed not to blink during the 20-second recording. For each subject, pupillary unrest was calculated twice as the difference between the maximum and minimum pupil size values. Pupillary unrest at each interval was compared using one-way analysis of variance, with the Tukey test for post hoc comparison. A p-value of <0.05 was considered statistically significant. We discovered pupillary unrest widening during the evening. Tukey test revealed significant differences between 07:00 and 19:00 (Evaluation 1, p < 0.01; Evaluation 2, p < 0.05) (Fig. 1A). The most remarkable result was that the natural light wavelength components peaked at around 450–480 nm in the daytime, while the greatest decrease in spectral radiant intensity (W/m2/μm) occurred in the evening (Fig. 1B,C). Netto et al. (2004) mentioned that the greatest variation in pupillary unrest occurred at the high-mesopic level of illumination, with a value of 0.31 mm. However, the detailed mechanism was still unknown. Ishikawa et al. (2012) reported that visual acuity and colour vision were not affected, whereas sustained pupil response became unstable with the 470-nm block filter. Therefore, we considered that the increase of pupillary unrest at 19:00 may be due to reduced activity of mRGCs. Consequently, the mRGC-mediated non-image forming vision is associated with wavelength components of natural light, which contain blue light at about 470 nm, even in the evening.