The process of photoentrainment, through the activation of photoreceptor transduction cascades, influences the circadian physiology of many life forms from primitive invertebrates to primates. In humans, a population of intrinsically photosensitive retinal ganglion cells (ipRGC's) is responsible for mediating the circadian rhythm and is susceptible to primary dysfunction affecting this cell population specifically, or disorders influencing light activation of retinal ganglion photoreceptors. The former may arise through cell depletion in conditions such as inherited or acquired optic neuropathies or conditions like Parkinson's disease which may alter retinal dopamine-mediated neurotransmission, and the latter, secondary to common causes of light transmission reduction associated with ageing and cataract. This review examines the current evidence linking ocular pathology and the resultant reduction in retinal phototransduction with circadian disturbances and sleep disorders, with downstream effects on our overall physiological integrity. As our understanding of the effects of light pathways on circadian biology develops, therapeutic modalities based upon the underlying pathophysiological processes are emerging, although the direct measurement, consequences and treatment of relative or absolute ipRGC dysfunction remain to be fully and clearly elucidated in man.
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