Suprachiasmatic nuclei (SCN) of the anterior hypothalamus serve as the body’s master biological clock.⁹ Ganglion photoreceptors send unconscious, non-visual photic information through the retinohypothalamic tract to the SCN permitting alignment of internal biological with external environmental time. They differ in many ways from the rods and cones that subserve conscious image-based vision.⁴ Ganglion photoreceptors require much more light to respond than cones and have thresholds well above those for photopic vision.^{2 9–11} They lack spatial resolution and can adapt to ambient lighting over days¹² and months.¹³ These properties are well suited to non-directional detection of gross environmental illumination essential for integrated circadian, neuroendocrine and neurobehavioural effects.⁴ Absent or deficient pRGC photoreception cannot be perceived subjectively,¹⁴ but ensuing circadian disturbances can have significant physiological and psychological consequences.^{15 16}

The SCN initiate events timed to allow preparation for impending metabolic, biochemical and physical activities.¹⁵ Prior to awakening, they activate a morning cortisol surge and trigger changes vital to transitioning from sleep to wakefulness.¹⁴ Morning exposure to sunlight increases core body temperature,¹⁷ alerting,¹⁸ cognition¹⁹ and brain serotonin levels²⁰ which enhance mood and vitality. As the day progresses, peak cognition occurs commensurate with maximal core body temperature. By evening, SCN actively inhibit cortisol secretion for recovery from the morning surge¹⁵ and initiate pineal secretion of the hormone melatonin which reduces alertness and decreases core body temperature.¹⁴ As sleep ensues, its slow wave stages and SCN suppression reduce cortisol to a healthy daily nadir as SCN orchestrate a nightly surge of melatonin and other sleep-related hormones.^{15 16 21}

Molecular mechanisms controlling self-sustaining SCN clock oscillations have been studied extensively.²² Similar mechanisms generating daily rhythms are present in most cells.²³ Peripheral cell oscillations quickly desynchronise with each other, however, unless constant temporal alignment is provided by the SCN’s neural and hormonal timing signals.^{22 23} Proper SCN functioning is critical for good health due to the numerous functions it coordinates.^{15 16 18 21 23 24} Without robust SCN signals, circadian rhythms of peripheral organs and cells can decouple, producing biochemical disarray and flattened rhythm amplitudes, and increasing risk of disease.^{15 25–27}

Melatonin produced by the pineal gland is the hormone most closely associated with SCN function.^{28 29} SCN neurons suppress or stimulate melatonin synthesis at appropriate times using a multisynaptic sympathetic pathway.^{28 30} Upregulation of the rate-limiting enzyme in melatonin synthesis (N-acetyltransferase) is directly and immediately suppressed by the SCN in response to light.^{10 28 31} Darkness therefore permits pineal melatonin production during the proper phase of the SCN cycle. Melatonin signals time of day and simultaneously provides potent antioxidant and numerous other beneficial effects.²⁸ Experimental nocturnal suppression of melatonin synthesis by light is the widely used surrogate for photic effects on SCN function.³²

The effectiveness of light exposure for pRGC-mediated biological effects depends on its intensity,³³ duration,³⁴ spectrum^{5 6} and timing relative to the phase of the circadian rhythm.³⁵ Internal biological clocks are entrained to external environmental time by timing cues known as zeitgebers.²⁸ Daily environmental light is by far the most important zeitgeber in humans,^{4 9 10 36} photoentraining the SCN to light–dark cycles. Suprathreshold early morning light advances, while evening light delays rhythms.³⁵

Sunlight has been the primary stimulus for pRGC photoreception throughout human history. Skylight has a dominant wavelength of 477 nm,³⁷ similar to peak pRGC sensitivity. Daylight illuminance can exceed 100 000 lux, as shown in fig 2. Contemporary artificial sources rarely provide more than 1% of the brightness of outdoor natural light,³⁸ with spectra shifted to longer (redder) wavelengths that are less effective for pRGC photoreception.³⁹

Brighter, longer, bluer light exposures are most efficient for retinal ganglion mediated effects including melatonin suppression,^{5 6} photoentrainment,⁴⁰ thermoregulation,¹⁷ improved nocturnal sleep quality,^41–43 heart-rate variability,¹⁷ treatment of non-seasonal⁴⁴ or seasonal depression,⁴⁵ enhanced mood/well-being,^{46 47} alertness,^{17 18 46 48} cognition,^{19 46 49} reaction time, performance and vigilance.^{18 48} The crystalline lens transmits progressively less visible light and particularly less blue light as it ages.^{50 51} Senescent miosis also progressively reduces retinal illumination.^{52 53} Deficient circadian photoreception results in significant neurobiological morbidity. We therefore examined how ageing and cataract surgery potentially affect the light available for circadian photoreception.

Table 1 presents relative effectiveness of circadian photoreception at different ages. By 45 years of age, crystalline lens yellowing and pupillary miosis reduces circadian photoreception to roughly half that of a 10-year-old. People in their eighth and ninth decades retain only 10% of a 10-year-old’s circadian photoreception, so they need 10 times more light for equivalent circadian photoreception under similar illumination, in agreement with Charman’s findings.⁵⁸ Deficits will be underestimates if pRGC populations decline with ageing as do those of non-photoreceptive retinal ganglion cells.⁵⁹ Additional reductions in pRGC photoreception may occur if ocular light transmission is decreased further by factors such as ethnicity, iris pigmentation,⁶⁰ reduced corneal clarity, cataract or sunglass usage.

SCN cycle at fixed, inherited, individually specific periods that typically differ from 24 h and average 24.2 h in humans.⁹ If environmental timing cues are inadequate or absent,^{36 65} SCN cycle daily at their own intrinsic period independent of geophysical day–night cycles. Repetitive cycling without daily resetting is termed free-running.⁹ In free-running, the phase of physiological cycles progressively deviates from and then returns to that of environmental day–night cycles over days or months.

Most totally blind individuals have abnormal or free-running circadian rhythms,^{36 66} but some visually blind individuals retain pRGC photoreception.⁶⁷ Visually blind people without pRGC photoentrainment suffer the additional burden of periodic extreme circadian desynchrony with daytime drowsiness from elevated daytime melatonin levels and night-time insomnia due to circadian alerting.⁶⁸ Their condition is equivalent to a lifetime of recurrent profound jetlag which in itself is disabling.⁶⁹ Blind individuals with intermittent insomnia and daytime napping despite adequate light exposure³⁶ should be suspected of free-running. They typically entrain with daily exogenous melatonin, which can improve their quality of life⁷⁰ and possibly reduce otherwise increased early mortality risks.^71–76

Inadequate environmental light exposure can also cause free-running circadian rhythms. People with normal vision in their mid-twenties free-run at room illuminances under 200 lux⁷⁷ or even 80 lux.⁷⁸ Astronauts (37–43 years of age) become free-running at typical space shuttle illuminances below 80 lux, producing circadian disruption, poor sleep quality and neurobehavioural performance decrements.⁶⁵ If 80–200 lux does not prevent free-running with its adverse consequences in 25-year-olds, much higher illuminances would be inadequate for older people with their declining crystalline lens transmittance and pupil area (cf, table 1). For example, 184–460, 256–640, 400–1000 and 536–1340 lux would be inadequate to prevent free-running in 55, 65, 75 and 85-year-old adults, respectively. Residential illuminances are much lower than those needed to prevent free-running in older adults, typically averaging only 100 lux (cf, fig 2).^{29 38 57} This light level is very dim compared with natural outdoor lighting.³⁹

Daily light exposures necessary for non-visual photoreception depend on numerous intrinsic^{13 60 79 80} and extrinsic factors.^{5 33–35} For example, older women even with dilated pupils are insensitive to blue light exposures sufficient to suppress melatonin significantly in younger women, demonstrating that age-related crystalline lens yellowing reduces circadian photoreception.⁸¹ As shown in fig 4, cataract surgery provides older adults with more youthful circadian photoreception.

Sunlight’s importance is underscored by seasonal and weather-related neuropsychological disorders that would not occur if indoor lighting were sufficient for all neurobiological needs. Midwinter insomnia affects up to 80% of certain populations at higher latitudes.⁸² Over 90% of people have some mood reduction during sporadically overcast weather or seasonal decreases in daylight length or intensity.^83–85 Seasonal affective disorder (SAD) causes disabling depression, hypersomnolence and weight gain during the fall and winter in approximately 10% of the population.⁸⁶ Non-seasonal depression is also closely associated with reduced light exposure.^{87 88} Reduced sunlight exposure in sighted individuals can cause insomnia, free-running rhythms, extreme flattening of hormonal profiles and cognitive difficulties that are reversible with restoration of adequate sunshine.^{89 90}

Environmental illumination is inversely correlated with insomnia^{42 91} and depression,^{87 88} both of which increase with ageing.⁹² Chronic sleep disturbances affect 40–70% of elderly populations.⁹² Indeed, only 12% of 9000 subjects aged 65 or older denied sleep complaints.⁹³ Chronic insomnia and depression are closely associated.^{93 94} Up to 30% of older populations have depression,^{95 96} which, like insomnia, frequently goes undiagnosed.^{97 98} Insomnia and depression are significant risk factors for cancer,⁹⁹ diabetes,¹⁰⁰ cognitive deficiencies,^{93 101} dementia,¹⁰² cardiovascular disease⁹⁵ and premature mortality.^{96 103} Flattened nocturnal melatonin amplitudes occur with ageing in some¹⁰⁴ but not all¹⁰⁵ people probably because of differences in environmental light exposure.⁴² Reduced circadian amplitudes are also associated with higher risks of cancer¹⁰⁶ and other diseases.¹⁰⁷ Bright light (2500 lux) particularly from bluer sources such as outdoor daylight can reduce or eliminate insomnia⁴² and depression;⁴⁴ immediately increase brain serotonin,²⁰ mood,⁴⁷ alertness, and cognitive function;^{17 19 49} and normalise otherwise decreased circadian hormonal amplitudes including nocturnal melatonin levels that may have been undetectable previously.^{42 89 90}