Human sensitivity to short-wavelength light in non-image-forming vision: Toward a mechanistic understanding of the impact of blue light on sleep and circadian rhythms (360G-Wellcome-204686_Z_16_Z)

Short-wavelength (blue) light takes priority in many functions associated with the non-image-forming (NIF) visual system, including pupil size and regulation of melatonin secretion. The human retina contains two short-wavelength sensitive photoreceptors: the blue-sensitive (S) cones (~440 nm) and the recently discovered photopigment melanopsin (~480 nm) expressed in a subset of retinal ganglion cells. Previous research has focused on the melanopsin contributions to NIF responses, but very little is known about how S cones contribute to and interact with melanopsin in these functions. Using the method of silent substitution which allows for the selective isolation of photoreceptor classes and by studying patient groups with S-cone anomalies, we will study the S cone and melanopsin inputs into pupil control and circadian mechanisms. In Aim 1, S cone and melanopsin inputs into the pupil will be characterised in controls and S-cone patients and related to sleep-wake actigraphy. In Aim 2, the spatial topography of S cone and melanopsin pupil inputs will be characterised using a novel spectral-spatial modulator. In Aim 3, S cone and melanopsin inputs into melatonin suppression will be characterised. In short, we will systematically characterise the receptor mechanisms that mediate the effect of short-wavelength light on circadian regulation in humans.