Melatonin Signaling Modulates Clock Genes Expression in the Mouse Retina

Abstract

Previous studies have shown that retinal melatonin plays an important role in the regulation of retinal daily and circadian rhythms. Melatonin exerts its influence by binding to G-protein coupled receptors named melatonin receptor type 1 and type 2 and both receptors are present in the mouse retina. Earlier studies have shown that clock genes are rhythmically expressed in the mouse retina and melatonin signaling may be implicated in the modulation of clock gene expression in this tissue. In this study we determined the daily and circadian expression patterns of Per1, Per2, Bmal1, Dbp, Nampt and c-fos in the retina and in the photoreceptor layer (using laser capture microdissection) in C3H-f+/+ and in melatonin receptors of knockout (MT1 and MT2) of the same genetic background using real-time quantitative RT-PCR. Our data indicated that clock and clock-controlled genes are rhythmically expressed in the retina and in the photoreceptor layer. Removal of melatonin signaling significantly affected the pattern of expression in the retina whereas in the photoreceptor layer only the Bmal1 circadian pattern of expression was affected by melatonin signaling removal. In conclusion, our data further support the notion that melatonin signaling may be important for the regulation of clock gene expression in the inner or ganglion cells layer, but not in photoreceptors.

The Circadian Clock Gene Bmal1 Controls Thyroid Hormone-Mediated Spectral Identity and Cone Photoreceptor Function

“…It has been demonstrated that in mice lacking both Per1 and Per2 , S opsin levels are reduced (Ait-Hmyed et al, 2013) and this phenotype is exactly opposite to our observations with Bmal1 deletion. Based on previous analysis (Hiragaki et al, 2014; Liu et al, 2012; Ruan et al, 2006), Per1 appears to be largely restricted to the INL while Per2 seems to be more cone specific, suggesting a distinct function for the different Per genes. To determine if photoreceptor specific loss of Per2 would have the opposite effects to the loss of Bmal1, we used a floxed allele for Per2 (Figure S5 A) and deleted Per2 using the Crx-Cre transgene (Figure S5 C).…”

“…REVERBα inhibits Bmal1 transcription, whereas RORα enhances it (McMahon et al, 2014; Tosini et al, 2008). Transcripts and proteins encoded by clock genes have been detected in the cells of the inner nuclear layer (INL), ganglion cell layer (GCL), retinal pigmented epithelium (RPE), in cones and at very low levels in rods (Hiragaki et al, 2014; Liu et al, 2012; Mustafi et al, 2013; Ruan et al, 2006). Nonetheless, their role in photoreceptor development and function has not been determined.…”

A congenic line of the C57BL/6J mouse strain that is proficient in melatonin synthesis

“…F1, double heterozygous for CBA alleles; N2*, maximum 1 CBAtype allele in either gene; N2**, double heterozygous for CBA-type alleles; N3, double homozygous for CBA-type alleles. The population variances are not significantly different (Brown-Forsythe test; F [5,15] = 2.402 [P = .0778]), but the population means are significantly different (one-way ANOVA: F [5,15] = 32.470 [P = 2.105E-8]). Tukey's post hoc analysis indicates that CBA and N3 groups are not statistically different to one another (P > .5), but each is different from the other 3 groups (ie, F1, N2*, and N2**) (P < .001); none of the F1, N2*, and N2** groups is significantly different from the 2 others (P > .05).…”

“…[5][6][7][8][9][10][11][12] It has been proposed that melatonin deficiency has a favorable impact on domestic mice in breeding colonies by eliminating the antigonadal action of melatonin. 5,12 Although both melatonin-proficient and melatonin-deficient strains have normal circadian rhythms of locomotor activity and quite similar circadian clock function, 12 subtle differences between the 2 groups have been reported, so that the full repertoire of circadian rhythms is incomplete or their amplitude altered, in melatonin-deficient strains [see for instance [13][14][15][16] ].…”

The Modulatable Stem Cell Niche: Tissue Interactions during Hair and Feather Follicle Regeneration

“…In mammals, studies on the weasel, mink and red deer who are short day breeders (<12 hours of light), suggest seasonal molting is mediated by melatonin, a major hormone rhythmically synthesized by the pineal gland [64–66]. Circadian rhythm regulation is achieved via melatonin's ability to manipulate expression of the clock genes [67,68]. Peripheral tissue “calendar cells” express high affinity melatonin receptors that are sensitive to the duration of melatonin exposure [69].…”