Abstract
Background Light exposure entrains the
circadian clock through the intrinsically photosensitive retinal
ganglion cells, which sense light in addition to the cones and rods. In
congenital achromatopsia (ACHM; prevalence 1:30-50,000), the cone system
is non-functional, resulting in severe light avoidance and photophobia
at daytime light levels. How this condition affects circadian and
neuroendocrine responses to light is not known.
Methods In genetically
confirmed ACHM patients (n=7; age 30-72 years; 6 women, 1 male), we
examined survey-assessed sleep/circadian phenotype (PSQI, ESS, MEQ,
MCTQ), self-reported visual function (NEI-VFQ-25), sensitivity to light
(VLSQ-8) and use of spectral filters that modify chronic light exposure.
In all but one patient, we measured rest-activity cycles using
actigraphy over 3 weeks and measured the melatonin phase angle of
entrainment using the dim-light melatonin onset (DLMO).
Results ACHM
patients experience a severely attenuated light-dark cycle due to severe
light sensitivity and habitual use of filters to reduce retinal
illumination. In aggregate, both MEQ and MCTQ indicated a tendency to
late chronotype. We found regular rest-activity patterns in all patients
and normal phase angles of entrainment in participants with a measurable
DLMO.
Conclusions Our results reveal that a
functional cone system and exposure to daytime light intensities are not
necessary for regular behavioural and hormonal entrainment, even when
survey-assessed sleep and circadian phenotype indicated a tendency for a
late chronotype and sleep problems in our ACHM cohort. Our results can
be explained by an adaptation mechanism in circadian photoreception
which adjusts to the range of habitual light exposures.
https://doi.org/10.5281/zenodo.4059767