The Intrinsically Photosensitive Retinal Ganglion Cell (ipRGC) Pathway and Its Role in Light-Induced Discomfort in Humans

Photophobia is a complex phenomenon defined by light-driven painful sensations; commonly associated with pathology. Although underlying mechanisms remain poorly understood and no objective assessment exists, growing evidence suggests that the melanopsin-containing intrinsically photosensitive retinal ganglion cell (ipRGC) light irradiance pathway plays a critical role in transducing light into a painful percept. The purpose of this thesis is to investigate the properties of the recently discovered ipRGC pathway and its role in mediating light-induced discomfort. Using chromatic pupillometry, Study 1 demonstrates that melanopsin-mediated ipRGC signals are summated binocularly, a fundamental extension of the current understanding of this pathway. Using a novel objective tool to quantify light-induced visual discomfort, Study 2 then provides in-vivo evidence linking perceptual experience with features of the melanopsin system, which may mediate photophobia. In sum, this thesis expands our current understanding of the melanopsin pathway, and provides novel tools to assess photophobia in different clinical populations.M.Sc