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

Shigekazu Higuchi,Akiko Hida,Akira Yasukouchi,Youhei Kinjyo,Sang-Il Lee,Manabu Miyahira,Kazuo Mishima,Sei-Ichi Tsujimura,Namni Goel

doi:10.1371/journal.pone.0060310

Abstract

BackgroundMelanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs) play an important role in non-image forming responses to light, such as circadian photoentrainment, light-induced melatonin suppression, and pupillary light response. Although it is known that there are some single nucleotide polymorphisms (SNPs) in the melanopsin (OPN4) gene in humans, the associations of the SNPs with non-image forming responses to light remains unclear. In the present study, we examined the associations of melanopsin gene polymorphisms with pupillary light response.MethodsJapanese university students (mean age: 21.0±1.7 years) with the genotypes of TT (n = 38), TC (n = 28) and CC (n = 7) at rs1079610 (I394T) located in the coding region participated in the present study. They were matched by age and sex ratio. Dark-adapted pupil size (<1 lx) was first measured. Then steady-state pupil size was measured during exposure to five lighting conditions (10 lx, 100 lx, 1000 lx, 3000 lx, 6000 lx in the vertical direction at eye level).ResultsSignificant interaction between the genotype of I394T (TT versus TC+CC) and luminance levels was found in pupil size. Under high illuminance levels (1000 lx, 3000 lx and 6000 lx), pupil sizes in subjects with the C allele were significantly smaller than those in subjects with the TT genotype. On the other hand, pupil size in subjects with the C allele under low illuminance (<1 lx) was significantly larger than that in subjects with the TT genotype. Percentages of pupil constriction under high illuminance levels were significantly greater in subjects with the C allele than in subjects with the TT genotype.ConclusionsHuman melanopsin gene polymorphism I394T interacted with irradiance in association with pupil size. This is the first evidence suggesting a functional connection between melanopsin gene polymorphism and pupillary light response as an index of non-image forming response to light.

Highlights

A new photoreceptor expressing the photopigment melanopsin was discovered in the mammalian outer retina and was named intrinsically photosensitive retinal ganglion cell [1]
The intrinsically photosensitive retinal ganglion cells (ipRGCs) detect irradiance of ambient light, and the signal is transmitted to the brain centers for non-image forming responses to light such as the suprachiasmatic nucleus (SCN), intergeniculate leaflet (IGL), and olivary pretectal nucleus (OPN) [2]
One study showed that a single nucleotide polymorphism (SNP) of the melanopsin gene was associated with prevalence of seasonal affective disorder (SAD) [10]

Summary

Introduction

A new photoreceptor expressing the photopigment melanopsin was discovered in the mammalian outer retina and was named intrinsically photosensitive retinal ganglion cell (ipRGC) [1]. The ipRGCs play important roles in circadian photoentrainment [3], pupillary light response [4,5], sleep [6,7] and other behavioral and physiological functions. It is known that a short photoperiod in winter increases the risk of SAD [11] Those studies suggest a functional connection between melanopsin gene polymorphism and phototransduction of a nonimage forming process, there is no evidence to connect them. Melanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs) play an important role in non-image forming responses to light, such as circadian photoentrainment, light-induced melatonin suppression, and pupillary light response. It is known that there are some single nucleotide polymorphisms (SNPs) in the melanopsin (OPN4) gene in humans, the associations of the SNPs with non-image forming responses to light remains unclear. We examined the associations of melanopsin gene polymorphisms with pupillary light response

Methods

Results

Conclusion