These alertness and performance profiles are similar to those experienced by extreme “morning” and “evening” types who also sleep and wake at relatively abnormal Alvespimycin price circadian phases.72 In free running subjects, the rhythms in alertness and performance also free-run, as first shown in the case by Miles et al,53 such that subjects report feeling the worst when awake at the time of peak aMT6s production

and best when awake at a normal circadian phase, when no aMT6s is being produced, as Inhibitors,research,lifescience,medical occurs in most sighted subjects. The effect of light in the blind The effect of visual impairment on circadian photoreception The impact of different types of visual impairment on the circadian system has been used as an indirect method to assess the photoreceptor systems mediating circadian and other nonvisual responses to light. Firstly, these studies have shown that eyes are required for circadian photoreception; individuals without eyes, either through bilateral enucleation or as

Inhibitors,research,lifescience,medical a result of developmental disorders, are unable to entrain their circadian pacemaker to the 24-hour light-dark cycle.61 Similarly, the majority Inhibitors,research,lifescience,medical of totally blind individuals who retain their eyes but cannot consciously perceive light also exhibit circadian rhythms that are not entrained to the 24-hour light-dark cycle, as described above. Disorders of the visual system do not always attenuate the circadian effects of light, however, demonstrating a functional separation of the Inhibitors,research,lifescience,medical visual and circadian photoreception systems. As outlined previously, the majority of legally blind individuals who retain some degree of light perception, even with very little usable vision in some cases, have normally entrained clrcadlan rhythms.61 Primary loss of the central or peripheral visual fields Is also not associated with circadian rhythm disorders,61,63 suggesting that the circadian photoreceptor system

Is less sensitive to the spatial distribution and Intensity of light than vision. Color Inhibitors,research,lifescience,medical blindness, a more specific lesion of the threecone photoplc visual system, also does not attenuate circadian responses to light, as measured by acute suppression of pineal melatonin,73 suggesting that the cones are not the primary photoreceptors mediating this response. Finally, and most definitively, Resminostat It has been demonstrated that a small proportion of blind people without light perception retain normal circadian phase-shifting and melatonin suppression responses to light, even In the absence of any func tlonal rods or cones, as assessed by conscious ability to detect light, visually-evoked potentials, or electroretinogram (Figure 5). 74,75 As expected If their eyes contained fully functional circadian photoreceptors, these Individuals exhibit normally entrained 24-hour rhythms under realworld conditions and do not report sleep disorders.