Melanopsin Gene Polymorphism I394T Is Associated with Pupillary Light Responses in a Dose-Dependent Manner

Higuchi, Shigekazu; Hida, Akiko; Tsujimura, Sei-ichi; Mishima, Kazuo; Yasukouchi, Akira; Lee, Sang il; Kinjyo, Youhei; Miyahira, Manabu

doi:10.1371/journal.pone.0060310

Cited by 24 publications

(26 citation statements)

References 39 publications

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“…Similarly, in our previous study, we found that OPN4 gene I394T differences in PLR were apparent under a high-illuminance light condition [21]. The results of the present study, obtained using a new sample population, strongly support the results of our previous study.…”

Section: Discussionsupporting

confidence: 92%

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Association between melanopsin gene polymorphism (I394T) and pupillary light reflex is dependent on light wavelength

Lee

Hida

Tsujimura

et al. 2013

J Physiol Anthropol

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BackgroundOur aim was to determine the association between melanopsin gene polymorphism and pupillary light reflex under diverse photic conditions, including different intensities and wavelengths.MethodsA total of 195 visually corrected subjects volunteered for investigation of the melanopsin gene of single nucleotide polymorphism (SNP) of rs1079610 (I394T). The genotype groups were TT (n = 126), TC (n = 55), and CC (n = 8), and 75 of the subjects, including subjects with TT (n = 34), TC (n = 33), and CC (n = 8) participated in our experiment. Three monochromatic lights with peak wavelengths of 465 nm (blue), 536 nm (green), and 632 nm (red) were prepared, and each light was projected to the subjects with five intensities, 12, 13, 14, 14.5 and 15 log photons/(cm2 s), for one minute. The pupil size of the left eye was measured under each light condition after a 1-minute adaptation.ResultsThe pupils of the TC + CC genotypes (n = 38) were significantly smaller than those of the TT genotype (n = 31) under a blue (463 nm) light condition with 15 log photons/(cm2 s) (P < 0.05). In contrast, there were no significant differences under green (536 nm) and red (632 nm) light conditions. Conversely, relative pupil constrictions of the TC + CC genotypes were greater than those of the TT genotype under both blue and green conditions with high intensities (14.5 and 15 log photons/(cm2 s)). In contrast, there were no significant differences between genotype groups in pupil size and relative pupilloconstriction under the red light conditions.ConclusionsOur findings suggest that the melanopsin gene polymorphism (I394T) functionally interacts with pupillary light reflex, depending on light intensity and, particularly, wavelength, and that under a light condition fulfilling both high intensity and short wavelength, the pupillary light response of subjects with the C allele (TC + CC) is more sensitive to light than that of subjects with the TT genotype.

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Section: Discussionsupporting

confidence: 92%

“…This recruitment was totally different from that in our previous study [21]. All subjects had normal color vision, as tested by the Ishihara color vision test.…”

Section: Methodsmentioning

confidence: 93%

Association between melanopsin gene polymorphism (I394T) and pupillary light reflex is dependent on light wavelength

Lee

Hida

Tsujimura

et al. 2013

J Physiol Anthropol

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“…One possible explanation to this phenomenon of normal sleep quality despite reduced melanopsin activity was proposed as the absence of the TT allele of the melanopsin gene (OPN4) (Adhikari et al 2016b). The TT genotype has been shown to be less sensitive to light and associated with disturbed sleep quality (Roecklein et al 2012;Higuchi et al 2013;Lee et al 2013Lee et al , 2014. The role of the TT genotype cannot be ruled out in our study.…”

Section: Discussionmentioning

confidence: 64%

Melanopsin‐mediated pupillary light reflex and sleep quality in patients with normal tension glaucoma

Ahmadi

Lund‐Andersen

Kolko

et al. 2019

Acta Ophthalmologica

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Purpose: The intrinsically photosensitive retinal ganglion cells (ipRGCs) and sleep quality are impaired in patients with primary open-angle glaucoma (POAG). In this study, we investigated whether ipRGCs and sleep quality were also impaired in patients with normal tension glaucoma (NTG). Methods: We performed pupillometry and sleep quality assessment in 15 patients with NTG and 17 healthy age-matched controls. Pupillometry protocol consisted of monocular stimulation with high illuminance (100 lux) red (633 nm, 300 cd/m 2 or 15.23 log quanta/cm 2 /s) and blue light (463 nm, 332 cd/m 2 or 15.27 log quanta/cm 2 /s) and binocular pupil measurements. Prior to light stimulation, patients were dark-adapted for 5 min. The late postillumination pupillary response (PIPR Late ) to blue light was used as marker of ipRGC activity. Sleep quality was assessed by Pittsburgh Sleep Quality Index (PSQI) questionnaire. Results: The PIPR Late to blue light was significantly reduced in patients with NTG compared to healthy subjects (p < 0.001), indicating impairment of the melanopsin-mediated pupillary pathway. There was no significant difference in the response elicited by red light (p = 0.6). Baseline pupil diameter and pupillary constriction amplitude to both red and blue light were reduced in patients with NTG (p < 0.05). The global score in PSQI was not significantly different between healthy controls and patients with NTG, indicating normal sleep quality (p = 0.6). Furthermore, we found no correlation between sleep parameters and pupillary light reflex parameters. Conclusion: Patients with NTG exhibited reduced ipRGC activity compared to healthy subjects, while no differences were observed in sleep quality.

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“…Additionally, a single nucleotide polymorphism on the melanopsin gene ( OPN4 ) was shown to relate to pupil size during light exposure (Higuchi et al . ). The potentially sustained constriction seen in our DSWPD patients may indicate an underlying increase in light signalling to the SCN after the light stimulus has ended, and therefore may be one of the physiological mechanisms underlying the greater phase shifting response seen in this group.…”

Section: Discussionmentioning

confidence: 99%

Increased sensitivity of the circadian system to light in delayed sleep–wake phase disorder

Watson

Phillips

Hosken

et al. 2018

The Journal of Physiology

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Key points This is the first study to demonstrate an altered circadian phase shifting response in a circadian rhythm sleep disorder. Patients with delayed sleep–wake phase disorder (DSWPD) demonstrate greater sensitivity of the circadian system to the phase‐delaying effects of light. Increased circadian sensitivity to light is associated with later circadian timing within both control and DSWPD groups. DSWPD patients had a greater sustained pupil response after light exposure. Treatments for DSWPD should consider sensitivity of the circadian system to light as a potential underlying vulnerability, making patients susceptible to relapse. Abstract Patients with delayed sleep–wake phase disorder (DSWPD) exhibit delayed sleep–wake behaviour relative to desired bedtime, often leading to chronic sleep restriction and daytime dysfunction. The majority of DSWPD patients also display delayed circadian timing in the melatonin rhythm. Hypersensitivity of the circadian system to phase‐delaying light is a plausible physiological basis for DSWPD vulnerability. We compared the phase shifting response to a 6.5 h light exposure (∼150 lux) between male patients with diagnosed DSWPD (n = 10; aged 20.8 ± 2.3 years) and male healthy controls (n = 11; aged 22.4 ± 3.3 years). Salivary dim light melatonin onset (DLMO) was measured under controlled conditions in dim light (<3 lux) before and after light exposure. Correcting for the circadian time of the light exposure, DSWPD patients exhibited 31.5% greater phase delay shifts than healthy controls. In both groups, a later initial melatonin phase was associated with a greater magnitude phase shift, indicating that increased circadian sensitivity to light may be a factor that contributes to delayed phase, even in non‐clinical groups. DSWPD patients also had reduced pupil size following the light exposure, and showed a trend towards increased melatonin suppression during light exposure. These findings indicate that, for patients with DSWPD, assessment of light sensitivity may be an important factor that can inform behavioural therapy, including minimization of exposure to phase‐delaying night‐time light.

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Melanopsin Gene Polymorphism I394T Is Associated with Pupillary Light Responses in a Dose-Dependent Manner

Cited by 24 publications

References 39 publications

Association between melanopsin gene polymorphism (I394T) and pupillary light reflex is dependent on light wavelength

Association between melanopsin gene polymorphism (I394T) and pupillary light reflex is dependent on light wavelength

Melanopsin‐mediated pupillary light reflex and sleep quality in patients with normal tension glaucoma

Increased sensitivity of the circadian system to light in delayed sleep–wake phase disorder

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