Kavita Thapan

An action spectrum for melatonin suppression: evidence for a novel non‐rod, non‐cone photoreceptor system in humans

1 Non‐image forming, irradiance‐dependent responses mediated by the human eye include synchronisation of the circadian axis and suppression of pineal melatonin production. The retinal photopigment(s) transducing these light responses in humans have not been characterised. 2 Using the ability of light to suppress nocturnal melatonin production, we aimed to investigate its spectral sensitivity and produce an action spectrum. Melatonin suppression was quantified in 22 volunteers in 215 light exposure trials using monochromatic light (30 min pulse administered at circadian time (CT) 16‐18) of different wavelengths (λmax 424, 456, 472, 496, 520 and 548 nm) and irradiances (0.7‐65.0 μW cm−2). 3 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. 4 The resulting action spectrum showed unique short‐wavelength sensitivity very different from the classical scotopic and photopic visual systems. The lack of fit (r2 < 0.1) of our 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 over the λmax range 420‐480 nm showed that rhodopsin templates between λmax 457 and 462 nm fitted the data well (r2≥ 0.73). Of these, the best fit was to the rhodopsin template with λmax 459 nm (r2= 0.74). 5 Our data strongly support a primary role for a novel short‐wavelength photopigment in light‐induced melatonin suppression and provide the first direct evidence of a non‐rod, non‐cone photoreceptive system in humans.

Light-induced melatonin suppression: age-related reduction in response to short wavelength light

One of the possible causes of disturbed circadian rhythms and sleep in the elderly may be impaired photic input to the circadian clock. Age-related changes in lens density are known to reduce the transmission of short wavelength light, which has been shown to be most effective in suppressing nocturnal melatonin. The aim of the study therefore was to investigate age-related changes in melatonin suppression in response to short and medium wavelength light. Young premenopausal (n=13) and postmenopausal (n=21) women were exposed to 30 min of monochromatic light at two different wavelengths and irradiances (lambda(max) 456 nm: 3.8 and 9.8 microW/cm(2); lambda(max) 548 nm: 28 and 62 microW/cm(2)). Melatonin suppression was compared across light treatments and between age groups. Significantly reduced melatonin suppression was noted in the elderly subjects following exposure to short wavelength (456 nm) light compared to the young subjects. These results are likely to reflect age-related changes in lens density.