Localization of a circadian clock in mammalian photoreceptors

Tosini, Gianluca; Davidson, Alec J.; Fukuhara, Chiaki; Kasamatsu, Manami; Castanon-Cervantes, Oscar

doi:10.1096/fj.07-8371com

Cited by 118 publications

(134 citation statements)

References 45 publications

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“…It is conceivable that only under certain pathological conditions of ischemia or hypoxia, RORa becomes highly induced to exert suppression on SEMA3E to result in exacerbation of pathological neovascularization, whereas under normal developmental conditions RORa is likely expressed only at a low basal levels that are not sufficient to significantly affect Sema3E expression and developmental retinal angiogenesis. In addition to RGCs, expression of RORa was identified in retinal photoreceptors (26,27) and macrophages/microglia (25). Whereas expression of RORa was reported in human vascular cells (61,62), previously we observed only low levels of RORa expression in retinal blood vessels.…”

Section: Discussionmentioning

confidence: 76%

“…Our previous study (25) showed that RORa is expressed in retinal macrophages and microglia and regulates pathological retinal angiogenesis by modulating SOCS3-dependent inflammation in a mouse model of oxygen-induced retinopathy (OIR), modeling retinopathy of prematurity and the proliferative aspects of diabetic retinopathy in humans. Other studies also identified RORa expression in retinal neurons, including RGCs and photoreceptors (21,26,27), yet whether RORa regulates expression of SEMA3s in the retinal neurons to affect retinal angiogenesis is not known.…”

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confidence: 99%

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RORα modulates semaphorin 3E transcription and neurovascular interaction in pathological retinal angiogenesis

et al. 2017

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Pathological proliferation of retinal blood vessels commonly causes vision impairment in proliferative retinopathies, including retinopathy of prematurity. Dysregulated crosstalk between the vasculature and retinal neurons is increasingly recognized as a major factor contributing to the pathogenesis of vascular diseases. Class 3 semaphorins (SEMA3s), a group of neuron-secreted axonal and vascular guidance factors, suppress pathological vascular growth in retinopathy. However, the upstream transcriptional regulators that mediate the function of SEMA3s in vascular growth are poorly understood. Here we showed that retinoic acid receptor-related orphan receptor a (RORa), a nuclear receptor and transcription factor, is a novel transcriptional regulator of SEMA3E-mediated neurovascular coupling in a mouse model of oxygen-induced proliferative retinopathy. We found that genetic deficiency of RORa substantially induced Sema3e expression in retinopathy. Both RORa and SEMA3E were expressed in retinal ganglion cells. RORa directly bound to a specific ROR response element on the promoter of Sema3e and negatively regulated Sema3e promoter-driven luciferase expression. Suppression of Sema3e using adeno-associated virus 2 carrying short hairpin RNA targeting Sema3e promoted disoriented pathological neovascularization and partially abolished the inhibitory vascular effects of RORa deficiency in retinopathy. Our findings suggest that RORa is a novel transcriptional regulator of SEMA3E-mediated neurovascular coupling in pathological retinal angiogenesis.-Sun, Y., Liu, C.-H., Wang, Z., Meng, S. S., Burnim, S. B., SanGiovanni, J. P., Kamenecka, T. M., Solt, L. A., Chen, J. RORa modulates semaphorin 3E transcription and neurovascular interaction in pathological retinal angiogenesis. FASEB J. 31, 4492-4502 (2017). www.fasebj.org

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Section: Discussionmentioning

confidence: 76%

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confidence: 99%

RORα modulates semaphorin 3E transcription and neurovascular interaction in pathological retinal angiogenesis

et al. 2017

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“…Many investigations have shown that retinal photoreceptors of vertebrates synthesize melatonin under the direct control of a circadian clock (2,3). In a few cases, the circadian pacemaker driving rhythmic melatonin synthesis has been localized to the photoreceptors themselves (2,4,5). In the retina melatonin levels are high during the night and low during the day and exposure to light during the night induces a rapid and dramatic decrease in the levels of melatonin (6,7).…”

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confidence: 99%

Melatonin modulates visual function and cell viability in the mouse retina via the MT1 melatonin receptor

Baba

Pozdeyev²,

Mazzoni³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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165

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A clear demonstration of the role of melatonin and its receptors in specific retinal functions is lacking. The present study investigated the distribution of MT1 receptors within the retina, and the scotopic and photopic electroretinograms (ERG) and retinal morphology in wildtype (WT) and MT1 receptor-deficient mice. MT1 receptor transcripts were localized in photoreceptor cells and in some inner retinal neurons. A diurnal rhythm in the dark-adapted ERG responses was observed in WT mice, with higher a-and b-wave amplitudes at night, but this rhythm was absent in mice lacking MT1 receptors. Injection of melatonin during the day decreased the scotopic response threshold and the amplitude of the a-and b-waves in the WT mice, but not in the MT1 ؊/؊ mice. The effects of MT1 receptor deficiency on retinal morphology was investigated at three different ages (3, 12, and 18 months). No differences between MT1 ؊/؊ and WT mice were observed at 3 months of age, whereas at 12 months MT1 ؊/؊ mice have a significant reduction in the number of photoreceptor nuclei in the outer nuclear layer compared with WT controls. No differences were observed in the number of cells in inner nuclear layer or in ganglion cells at 12 months of age. At 18 months, the loss of photoreceptor nuclei in the outer nuclear layer was further accentuated and the number of ganglion cells was also significantly lower than that of controls. These data demonstrate the functional significance of melatonin and MT1 receptors in the mammalian retina and create the basis for future studies on the therapeutic use of melatonin in retinal degeneration.electroretinogram ͉ neuroprotection ͉ visual sensitivity ͉ glaucoma

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“…[16] Their input synchronizes the SCN to maintain the circadian rhythm near a 24 h cycle by driving the nocturnal synthesis of the pineal hormone National Journal of Physiology, Pharmacy and Pharmacologymelatonin and feedback loops to mediate clock information to the peripheral tissues and induce circadian phase, sleep, and maintenance of pupil diameter. [17,18] Hence, melanopsin which has a role in the maintenance of pupil diameter [19][20][21][22] and providing the primary environmental light input to the SCN for photoentrainment of the circadian rhythm might be affected. A constricted pupil may decrease the area of retinal illumination and increase the average latency of P100.The average decrease in pupillary diameter of 1.75 mm increases the average latency by 4.6 ms. [1] Our finding also supports the result of Jackson et al, [23] who observed the increase in P100 latency and reduction in amplitude in professional drivers with sleep deprivation.…”

Section: Discussionmentioning

confidence: 99%

Visual evoked potential changes among security guards of Government Medical College and New Civil Hospital, Surat

Devalia¹,

Mathur²,

Chhaya³

et al. 2017

Natl J Physiol Pharm Pharmacol

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Background: Sleep interruption and disturbance of circadian rhythm are inevitable phenomena among night shift workers. A very few evidence is available that describing effects of sleep disturbance and its effect on the visual pathway by measuring the visual evoke potential parameters. Aims and Objectives: To study the change in visual evoked potential (VEP) due to disturbance of circadian rhythm among rotating shift workers. Materials and Methods: This cross-sectional study was done on 80 security guards of 20-40 years of age working in Government Medical College and New Civil Hospital of Surat. They were divided into two groups comprising of 40 participants. Group 1 comprised of 40 security guards who did rotating night shift for more than 6 months and Group 2 include 40 security guards who did not perform any night shift duty for the past 2 years. VEP test was done, and results of both groups were compared with each other. Result: The result showed that there was statistically significant (P < 0.05) prolongation of P100 latency in rotating shift workers compared to day workers. The amplitude of P100 decreases in shift worker while comparing both the groups, but it was statistically insignificant (P > 0.05). Pearson correlation revealed, as the head circumference increases, latency of VEP increases, and amplitude decreases. Conclusion: Alteration in circadian rhythm affected the parameters of VEP in a negative way. In long-term, it may impair their general health. Furthermore, further study is required to support this conclusion.

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Localization of a circadian clock in mammalian photoreceptors

Cited by 118 publications

References 45 publications

RORα modulates semaphorin 3E transcription and neurovascular interaction in pathological retinal angiogenesis

RORα modulates semaphorin 3E transcription and neurovascular interaction in pathological retinal angiogenesis

Melatonin modulates visual function and cell viability in the mouse retina via the MT1 melatonin receptor

Visual evoked potential changes among security guards of Government Medical College and New Civil Hospital, Surat

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