Using Light to Promote Sleep & Circadian Rhythms

Abstract

A subset of retinal ganglion cells expresses the photopigment melanopsin and is thus photosensitive. These intrinsically photosensitive retinal ganglion cells (ipRGCs) integrate inputs from rods and cones as well as from melanopsin. Recent research has shown the variety of visual and non-image forming (NIF) responses that ipRGCs contribute to. However, there is uncertainty around the degree to which these responses arise from melanopsin compared to rods and cones, and how the diversity in ipRGCs supports these functions. This is, in part, due to a limitation in tools to assess melanopsin contribution in humans. By developing our understanding of melanopsin in vision and behaviour, we can better understand the impact of our lighting environment on our physiology and make improvements to advance human health and wellbeing. IpRGCs are a heterogeneous population, with six subtypes in mice varying in morphology and electrophysiology. Research suggests all subtypes are involved in vision, via projections to the dorsal lateral geniculate nucleus (dLGN). However, little is known of the relative contributions of the different ipRGC subtypes to the dLGN projection. We assessed this using the multilabelling technique of brainbow in dLGN-projecting ipRGCs. We find five subtypes involved in these projections and restricted topography of labelled cells in the retina. These results suggest that the diversity in ipRGCs is harnessed to support the function of vision. Assessing melanopsin contribution to responses in humans relies on visual display units (VDUs). The technique of silent substitution allows for the targeted stimulation of melanopsin, whilst excitation for other receptors remains constant. This is achieved through the presentation of metameric stimuli, often incorporating a cyan primary due to melanopsin's peak sensitivity. We discover a visual anomaly of Maxwell's spot in stimuli when the cyan primary is employed. We characterise the stimuli that elicit Maxwell's spot and identify a constraint during stimuli generation that minimises its appearance. This can help create visually uniform metameric stimuli for use in melanopsin research. Many existing VDUs for assessing melanopsin in humans have limitations in contrast, spatial resolution, practicality, and relevance in the modern screen-based world. We developed and categorised a new tool for use in vision research. Our multiprimary VDU can present metameric stimuli that vary substantially in melanopsin excitation. We identify some limitations and offer suggestions for the future development of VDUs for use in vision research. Ambient lighting has an impact on human cognition. However, most studies have been conducted in the lab and have limited application to the real world. We developed a new research tool: an app, able to present performance-measuring tasks whilst recording illuminance. We implement this app to determine the effects of illuminance and time of day on performance in the field. We identify several significant relationships that confirm laboratory findings, as well as new results for the effects of lighting, time of day and subjective sleepiness on visual search. With this new tool, there is a vast avenue of research questions that can be addressed in the context of human cognition in the real world.

Date of Award	1 Aug 2022
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Timothy Brown (Supervisor), Robert Lucas (Supervisor) & Annette Allen (Supervisor)