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The Special Sensitivity of Light-Induced Melatonin Suppression in Humans.

Thapan, Kavita. (2001) The Special Sensitivity of Light-Induced Melatonin Suppression in Humans. Doctoral thesis, University of Surrey (United Kingdom)..

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Abstract

The eye is a complex organ involved in the input pathway of circadian entrainment. Non-image forming, irradiance-dependent responses mediated by the human eye include synchronisation of the circadian axis and suppression of pineal melatonin production. Light exposure at night causes an acute suppression of melatonin levels. In humans the photoreceptors mediating this and other circadian responses to light are not known. Identification of a photopigment requires an investigation of the spectral sensitivity (action spectrum) of the light-dependent response. The aim of this thesis was to construct an action spectrum for light-induced melatonin suppression. Melatonin suppression was quantified in 22 volunteers in 215 light exposure trials using monochromatic light (30 minute pulse administered at circadian time (CT) 16-18) of different wavelengths (max 424, 456, 472, 496, 520 and 548 nm) and irradiances (0.7-65.0 μW/cm2). At each wavelength, suppression of plasma melatonin increased with increasing irradiance. Irradiance response curves (IRCs) were fitted and the generated half-maximal responses (IR50) were corrected for lens filtering and used to construct an action spectrum. The resulting action spectrum showed unique short-wavelength sensitivity very different to the classical scotopic and photopic visual systems. The lack of fit (R2<0.1) of the action spectrum with the published rod and cone absorption spectra precluded these photoreceptors from having a major role. Cryptochromes 1 and 2 also had a poor fit to the data. Fitting a series of Dartnall nomograms generated for rhodopsin-based photopigments showed that rhodopsin templates between max 457-462 nm fit the lens corrected data well (R2 > 0.73). Of these, the best fit was to the rhodopsin template with max 459 nm (R2 = 0.74). The findings demonstrate that short wavelength light is the most effective at suppressing melatonin and this sensitivity is clearly not matched to the spectral sensitivities of the known retinal photoreceptors that mediate human vision. As well as providing evidence for a novel photoreceptor system in humans, these data will allow optimisation of the spectral composition of light needed to manipulate the circadian axis.

Item Type: Thesis (Doctoral)
Divisions : Theses
Authors : Thapan, Kavita.
Date : 2001
Additional Information : Thesis (Ph.D.)--University of Surrey (United Kingdom), 2001.
Depositing User : EPrints Services
Date Deposited : 14 May 2020 14:56
Last Modified : 14 May 2020 15:00
URI: http://epubs.surrey.ac.uk/id/eprint/856701

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