Abstract
The absence of circadian zeitgebers in the social environment causes circadian misalignment, which is often associated with sleep disturbances. Circadian misalignment, defined as a mismatch between the sleep-wake cycle and the timing of the circadian system, can occur either because of inadequate exposure to the light-dark cycle, the most important synchronizer of the circadian system, or reduction in light transmission resulting from ophthalmic diseases (e.g., senile miosis, cataract, diabetic retinopathy, macular degeneration, retinitis pigmentosa, and glaucoma). We propose that glaucoma may be the primary ocular disease that directly compromises photic input to the circadian time-keeping system because of inherent ganglion cell death. Glaucomatous damage to the ganglion cell layer might be particularly harmful to melanopsin. According to histologic and circadian data, a subset of intrinsically photoresponsive retinal ganglion cells, expressing melanopsin and cryptochromes, entrain the endogenous circadian system via transduction of photic input to the thalamus, projecting either to the suprachiasmatic nucleus or the lateral geniculate nucleus. Glaucoma provides a unique opportunity to explore whether in fact light transmission to the circadian system is compromised as a result of ganglion cell loss.
Highlights
Light in human physiology Numerous experimental studies have convincingly shown that light is the most important synchronizer of circadian rhythms [1]
Consistent with established phase response curves, light exposure early in the morning resets the circadian system to adjust for its propensity to phasedelay, and light exposure in the evening is necessary to adjust for phase-advances in the master clock [2,3,4,5,6]
Reduced axonal stimulation to the central visual pathways likely diminishes light input to the circadian system. This is supported by recent evidence that melanopsin, which is found in retinal ganglion cells, is a major photopigment involved in circadian entrainment [59,60,61]
Summary
Light in human physiology Numerous experimental studies have convincingly shown that light is the most important synchronizer of circadian rhythms [1]. Reduced axonal stimulation to the central visual pathways likely diminishes light input to the circadian system This is supported by recent evidence that melanopsin, which is found in retinal ganglion cells, is a major photopigment involved in circadian entrainment [59,60,61]. Important were the finding of reduced retinal ganglion cells in two patients with glaucoma and the observation that melanopsin was conserved in retinae of blind patients with degeneration of the outer and/or inner layers These findings should be replicated in largescale studies before definitive conclusions can be reached. Http://www.jcircadianrhythms.com/content/6/1/1 early detection of glaucoma, as treatment will halt further optic nerve damage and may help preserve circadian photo-entrainment
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