SummaryPhotoreception in the mammalian retina is not restricted to rods and cones but extends to a small number of intrinsically photoreceptive retinal ganglion cells (ipRGCs), expressing the photopigment melanopsin [1–4]. ipRGCs are known to support various accessory visual functions including circadian photoentrainment and pupillary reflexes. However, despite anatomical and physiological evidence that they contribute to the thalamocortical visual projection [5–7], no aspect of visual discrimination has been shown to rely upon ipRGCs. Based on their currently known roles, we hypothesized that ipRGCs may contribute to distinguishing brightness. This percept is related to an object's luminance—a photometric measure of light intensity relevant for cone photoreceptors. However, the perceived brightness of different sources is not always predicted by their respective luminance [8–12]. Here, we used parallel behavioral and electrophysiological experiments to first show that melanopsin contributes to brightness discrimination in both retinally degenerate and fully sighted mice. We continued to use comparable paradigms in psychophysical experiments to provide evidence for a similar role in healthy human subjects. These data represent the first direct evidence that an aspect of visual discrimination in normally sighted subjects can be supported by inner retinal photoreceptors.

A clinical evaluation of the Shin-Nippon SRW-5000 (Japan), a newly released commercial autorefractor, was undertaken to assess its repeatability and validity compared to subjective refraction. Measurements of refractive error were performed on 200 eyes of 100 subjects (aged 24.4 +/- 8.0 years) subjectively (non-cycloplegic) by one optometrist and objectively with the SRW-5000 autorefractor by a second. Repeatability was assessed by examining the differences between the seven autorefractor readings taken from each eye and by re-measuring the objective prescription of 50 eyes at a subsequent session. Although the SRW-5000 read slightly more plus than subjective refraction (mean spherical equivalent +0.16 +/- 0.44 D), it was found to be highly valid (accurate) compared to subjective refraction and repeatable over the prescription range of +6.50 to -15.00 D examined. The Shin-Nippon SRW-5000 autorefractor is therefore a valuable complement to subjective refraction and as it offers the advantage of a binocular open field-of-view, has a great potential benefit for accommodation research studies.

The recent discovery of melanopsin-containing retinal ganglion cells (mRGCs) has led to a fundamental reassessment of non-image forming processing, such as circadian photoentrainment and the pupillary light reflex. In the conventional view of retinal physiology, rods and cones were assumed to be the only photoreceptors in the eye and were, therefore, considered responsible for non-image processing. However, signals from mRGCs contribute to this non-image forming processing along with cone-mediated luminance signals; although both signals contribute, it is unclear how these signals are summed. We designed and built a novel multi-primary stimulation system to stimulate mRGCs independently of other photoreceptors using a silent-substitution technique within a bright steady background. The system allows direct measurements of pupillary functions for mRGCs and cones. We observed a significant change in steady-state pupil diameter when we varied the excitation of mRGC alone, with no change in luminance and colour. Furthermore, the change in pupil diameter induced by mRGCs was larger than that induced by a variation in luminance alone: that is, for a bright steady background, the mRGC signals contribute to the pupillary pathway by a factor of three times more than the L-and M-cone signals.

A newly released commercial autorefractor, the Shin-Nippon SRW-5000 (Japan), has been found to be valid compared to subjective refraction and repeatable over a wide prescription range. Its binocular open field-of-view allows the accommodative state to be monitored while a natural environment is viewed. In conventional static mode, the device can take up to 45 readings in 1 min using digital image analysis of the reflected retinal image of a measurement ring. Continuous on-line analysis of the ring provides high (up to 60 Hz) temporal resolution of the refractive state to an accuracy of < 0.001 D. Pupil size can also be analysed to a resolution of < 0.001 mm. The measurement of accommodation and pupil size was relatively unaffected by eccentricity of viewing up to +/- 10 degrees and instrument focusing inaccuracies of +/- 5 mm. The resolution properties of the analysis are shown to be ideal for measurement of dynamic accommodation and pupil responses.

In the retina, intrinsically photosensitive retinal ganglion cells (ipRGCs) which express photopigment melanopsin have been identified as photoreceptors which differ from cones and rods. It has been established that such melanopsin-expressing RGCs are involved in the circadian photo-entrainment and pupillary light reflexes. An additional projection from ipRGCs to the lateral geniculate nucleus has been identified, which indicates the association of ipRGCs with visual perception induced by the image-forming pathway. Reportedly, ipRGCs modulate brightness perception but quantitative analysis of brightness perception involving melanopsin and cones-based signals has not been elucidated. We conducted brightness perception experiments that involved melanopsin using a novel projector with six primary colors and formulated the results for melanopsin and cone stimuli. The white visual stimuli (5 degrees in size) that we used had a single xy-chromaticity values but melanopsin stimuli were modulated by designing different spectral distributions. Perceived brightness was measured using a magnitude estimation method at several luminance levels in the near periphery (7 degrees). Additionally, pupil diameter was measured for estimating the intensity of visual stimuli on the retina. The results showed that the perceived brightness of a white visual stimulus with different spectral distributions can be described by a summation of the nearly linear melanopsin response and the non-linear cone response with weighted coefficients, and the contribution ratio of melanopsin in brightness perception increased to 50% and more with increasing visual stimulus. These suggest that melanopsin signals play a crucial role in the estimation of the absolute intensity of the light environment by obtaining absolute brightness information even when cones are adapted by light.