Retinal Circadian Rhythms in Humans*

Tuunainen, Arja; Kripke, Daniel F.; Cress, Anthony C.; Youngstedt, Shawn D.

doi:10.1081/cbi-100107971

Cited by 20 publications

(17 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The calcium influx through L-type VGCCs is sufficient to trigger sustained glutamate release from photoreceptors (Schmitz and Witkovsky 1997), even though it is evident that cGMP-gated cation channels may play a supporting role in glutamate release (Rieke and Schwartz 1994). Circadian rhythms are evident in electroretinograms recorded from different species, including humans (Manglapus et al 1998;Tuunainen et al 2001;Miranda-Anaya et al 2002;Ren and Li 2004;Peters and Cassone 2005), which indicates that the release of glutamate from photoreceptors and photosensitivity could well be under circadian control. In addition, photoreceptors are more susceptible to intense light damage at night than during the day (Vaughan et al 2002).…”

Section: Discussionmentioning

confidence: 97%

“…The results from Hull et al do not establish a circadian control mechanism, because the cells were isolated from animals kept in LD cycles. However, it is certainly possible that the circadian regulation of L-type VGCCs we observe in photoreceptors may be a more general phenomenon, especially given that several components of the electroretinograms recorded from different species, including humans, display circadian rhythms (Manglapus et al 1998;Tuunainen et al 2001;Miranda-Anaya et al 2002;Ren and Li 2004;Peters and Cassone 2005).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The expression of L‐type voltage‐gated calcium channels in retinal photoreceptors is under circadian control

Ko¹,

Liu²,

Dryer³

et al. 2007

Journal of Neurochemistry

202

View full text Add to dashboard Cite

Photoreceptors are non-spiking neurons, and their synapses mediate the continuous release of neurotransmitters under the control of L-type voltage-gated calcium channels (VGCCs). Photoreceptors express endogenous circadian oscillators that play important roles in regulating photoreceptor physiology and function. Here, we report that the L-type VGCCs in chick cone photoreceptors are under circadian control. The L-type VGCC currents are greater when measured during the subjective night than during the subjective day. Using antibodies against the VGCCa1C and VGCCa1D subunits, we found that the immunofluorescence intensities of both VGCCa1C and VGCCa1D in photoreceptors are higher during the subjective night. However, the mRNA levels of VGCCa1D, but not VGCCa1C, are rhythmic. Nocturnal increases in L-type VGCCs are blocked by manumycin A, PD98059, and KN93, which suggest that the circadian output pathway includes Ras, Erk, and calcium-calmodulin dependent kinase II. In summary, four independent lines of evidence show that the L-VGCCs in cone photoreceptors are under circadian control. Keywords: avian, circadian, photoreceptor, retina, voltagegated calcium channel. Visual systems must anticipate daily changes in ambient illumination over 10-12 orders of magnitude. Circadian oscillators in the retina provide a mechanism for visual systems to initiate more sustained adaptive changes throughout the course of the day (Cahill and Besharse 1995;Green and Besharse 2004). The circadian oscillators in photoreceptors are endogenous and able to function independently in the absence of other retinal inputs (Cahill and Besharse 1993;Thomas et al. 1993;Ko et al. 2001). Photoreceptor circadian oscillators regulate retinomotor movement (Pierce and Besharse 1985;Burnside 2001), outer segment disc shedding and membrane renewal (LaVail 1980;Besharse and Dunis 1983), morphological changes at synaptic ribbons (Adly et al. 1999), gene expression (Korenbrot and Fernald 1989;Pierce et al. 1993;Haque et al. 2002), and the gating behavior of ion channels (Ko et al. 2001) among other photoreceptor activities. Importantly, photoreceptors are more sensitive to intense light damage at night than during the day, even in animals that have been maintained in constant darkness (DD) for several days after circadian lightdark (LD) cycle entrainment (Vaughan et al. 2002).Photoreceptors are non-spiking neurons, and they release glutamate continuously in the darkness as a result of depolarization-evoked activation of L-type voltage-gated calcium channels (VGCCs) (Barnes and Kelly 2002). The synthesis and release of the neurohormone melatonin in photoreceptors is also under circadian control (Cahill and Besharse 1993;Bernard et al. 1997;Ivanova and Iuvone 2003b), and melatonin synthesis and release can be blocked by dihydropyridine inhibitors of L-type VGCCs (Iuvone and Besharse 1986;Ivanova and Iuvone 2003a). In this regard, we previously showed that there is a circadian regulation of the apparent affinity of cGMP-gated ion channels (CNGCs) for cG...

show abstract

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

The expression of L‐type voltage‐gated calcium channels in retinal photoreceptors is under circadian control

Ko¹,

Liu²,

Dryer³

et al. 2007

Journal of Neurochemistry

202

View full text Add to dashboard Cite

show abstract

“…Earlier studies in humans showed a daily variation in retinal visual sensitivity, suggesting lower sensitivities in the early morning. [7][8][9] Besides a daily variation, a seasonal (circannual) variation might also be present. After all, exposure to light varies per season and prior light history affects light sensitivity.…”

Section: Methodsmentioning

confidence: 99%

“…6 Several researchers examined circadian rhythms in visual thresholds. [7][8][9]12,29 Although the confidence intervals were wide, retinal sensitivity seemed to be the lowest in the early morning. We found the lowest sensitivity directly after lunch and, in a subgroup of patients with early glaucoma, the highest sensitivity in the early morning.…”

Section: Time Of Daymentioning

confidence: 99%

Factors That Influence Standard Automated Perimetry Test Results in Glaucoma: Test Reliability, Technician Experience, Time of Day, and Season

Montolio

Wesselink

Gordijn

et al. 2012

Invest. Ophthalmol. Vis. Sci.

102

View full text Add to dashboard Cite

PURPOSE.To determine the influence of several factors on standard automated perimetry test results in glaucoma.METHODS. Longitudinal Humphrey field analyzer 30-2 Swedish interactive threshold algorithm data from 160 eyes of 160 glaucoma patients were used. The influence of technician experience, time of day, and season on the mean deviation (MD) was determined by performing linear regression analysis of MD against time on a series of visual fields and subsequently performing a multiple linear regression analysis with the MD residuals as dependent variable and the factors mentioned above as independent variables. Analyses were performed with and without adjustment for the test reliability (fixation losses and false-positive and false-negative answers) and with and without stratification according to disease stage (baseline MD).RESULTS. Mean follow-up was 9.4 years, with on average 10.8 tests per patient. Technician experience, time of day, and season were associated with the MD. Approximately 0.2 dB lower MD values were found for inexperienced technicians (P < 0.001), tests performed after lunch (P < 0.001), and tests performed in the summer or autumn (P < 0.001). The effects of time of day and season appeared to depend on disease stage. Independent of these effects, the percentage of false-positive answers strongly influenced the MD with a 1 dB increase in MD per 10% increase in false-positive answers. The variability of SAP test results depends on many factors. A well-known factor is disease stage. 1,2 Other factors are patient motivation and technician performance, the latter via appropriateness of refraction and patient instruction, reassurance before the test, and patient monitoring during the test. [3][4][5] Circadian rhythms and seasonal influences may also contribute to the variability. These periodicities may influence SAP test results in at least two different ways. First, patients need a good cognitive function to perform perimetry. In an extensive review, Blatter et al. 6 described a daily variation in cognitive function in humans. Cognitive function deteriorated over the day in the elderly (at the typical age of a glaucoma patient), whereas the opposite is the case in young subjects. Second, SAP measures a threshold sensitivity of the visual system. Earlier studies in humans showed a daily variation in retinal visual sensitivity, suggesting lower sensitivities in the early morning. CONCLUSIONS.7-9 Besides a daily variation, a seasonal (circannual) variation might also be present. After all, exposure to light varies per season and prior light history affects light sensitivity.10 Indeed, retinal sensitivity seems to be highest in the spring. 11,12 Variability is entangled with reliability, which is commonly assessed by reliability indices and displayed as the percentages of fixation losses (FL) and false-positive (FP) and false-negative (FN) answers. Two issues concerning reliability are relevant to this study. First, whether reliability as assessed by the reliability indices influences variability. Se...

show abstract

“…Two studies have addressed the question of whether ERG indices in humans undergo circadian rhythmicity, and both have shown somewhat lower ERG responses during the night and early morning compared to daytime and evening (Nozaki et al, 1983;Tuunainen et al, 2001). These studies used a single flash intensity (which probed in fact mixed rod-cone functions) and were not performed in prolonged darkness.…”

Section: Introductionmentioning

confidence: 97%

Human Retinal Light Sensitivity and Melatonin Rhythms Following Four Days in Near Darkness

Danilenko

Plisov

Wirz‐Justice³

et al. 2009

Chronobiology International

View full text Add to dashboard Cite

The rods in the retina are responsible for night vision, whereas the cone system enables day vision. We studied whether rod function in humans exhibits an endogenous circadian rhythm and if changes occur in conditions of prolonged darkness. Seven healthy subjects (mean age+/-SD: 25.6+/-12.3 yr) completed a 4.5-day protocol during which they were kept in complete darkness (days 1 and 4) and near darkness (<0.1 lux red light, days 2 and 3). Electroretinography (ERG) and saliva collections were done at intervals of at least 3 h for 27 h on days 1 and 4. Full-field ERGs were recorded over 10 low-intensity green light flashes known to test predominantly rod function. As a circadian marker, salivary melatonin concentration was measured by radioimmunoassay. The ERG data showed that rod responsiveness to light progressively diminished in darkness (significantly lower a- and b-wave amplitudes, longer b-wave implicit time). The decrease in amplitude (b-wave) from day 1 to day 4 averaged 22+/-14%. After correction for the darkness-related linear trend, the circadian variations in ERG indices were weak and usually non-significant, with slightly higher responsiveness to light during the day than night. Rod sensitivity (by K index) tended to decrease. Strikingly, the overall amount of melatonin secretion (area under 24 h curve) also decreased from day 1 to day 4 by 33.1+/-18.9% (p=.017). The drift of the melatonin rhythm phase was within the normal range, less than 56 min over three days. There was no significant correlation between the changes in ERG responses and melatonin. In conclusion, scotopic retinal response to (low-intensity) light and the amount of melatonin secreted are diminished when humans are kept in continuous darkness. Both processes may have a common underlying mechanism implicating a variety of neurochemicals known to be involved in the regulation of both photoreceptor and pineal gland function.

show abstract

Retinal Circadian Rhythms in Humans*

Cited by 20 publications

References 32 publications

The expression of L‐type voltage‐gated calcium channels in retinal photoreceptors is under circadian control

The expression of L‐type voltage‐gated calcium channels in retinal photoreceptors is under circadian control

Factors That Influence Standard Automated Perimetry Test Results in Glaucoma: Test Reliability, Technician Experience, Time of Day, and Season

Human Retinal Light Sensitivity and Melatonin Rhythms Following Four Days in Near Darkness

Contact Info

Product

Resources

About