Rainer Spessert

University Medical Center of the Johannes Gutenberg University Mainz

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Lutz Vollrath

Johannes Gutenberg University Mainz

Tanja Wolloscheck

Johannes Gutenberg University Mainz

Lydia Engel

Johannes Gutenberg University Mainz

Isabella Spiwoks‐Becker

Johannes Gutenberg University Mainz

Stefanie Kunst

Johannes Gutenberg University Mainz

Elisabeth Layes

Johannes Gutenberg University Mainz

Nils H. Rohleder

Technical University of Munich

Gianluca Tosini

Morehouse School of Medicine

Debra K. Kelleher

University Medical Center of the Johannes Gutenberg University Mainz

Heike Holthues

Frankfurt University of Applied Sciences

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Johannes Gutenberg University Mainz

University Medical Center of the Johannes Gutenberg University Mainz

Heidelberg University

Friedrich Schiller University Jena

Jena University Hospital

GlaxoSmithKline (Italy)

Max Planck Society

Charité - Universitätsmedizin Berlin

Leibniz Institute for Neurobiology

Consejo Nacional de Investigaciones Científicas y Técnicas

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Rhythmic Regulation of Photoreceptor and RPE Genes Important for Vision and Genetically Associated With Severe Retinal Diseases

Investigative Ophthalmology & Visual Science (2018)

Patrick Vancura Erika Csicsely Annalisa Leiser P. Michael Iuvone Rainer Spessert

Purpose: The aim of the present study was to identify candidate genes for mediating daily adjustment of vision. Methods: Genes important for vision and genetically associated with severe retinal diseases were tested for 24-hour rhythms in transcript levels in neuronal retina, microdissected photoreceptors, photoreceptor-related pinealocytes, and retinal pigment epithelium-choroid (RPE-choroid) complex by using quantitative PCR. Results: Photoreceptors of wildtype mice display circadian clock-dependent regulation of visual arrestins (Arr1, Arr4) and the visual cycle gene Rdh12, whereas cells of the RPE-choroid exhibit light-dependent regulation of the visual cycle key genes Lrat, Rpe65, and Rdh5. Clock-driven rhythmicity of Arr1, Arr4, and Rdh12 was observed also in rat pinealocytes, to persist in a mouse model of diabetic retinopathy (db/db) and, in the case of Arr1, to be abolished in retinae of mice deficient for dopamine D4 receptors. Therefore, the expression rhythms appear to be evolutionary conserved, to be unaffected in diabetic retinopathy, and, for Arr1, to require dopamine signaling via dopamine D4 receptors. Conclusions: The data of the present study suggest that daily adjustment of retinal function combines clock-dependent regulation of genes responsible for phototransduction termination (Arr1, Arr4) and detoxification (Rdh12) in photoreceptors with light-dependent regulation of genes responsible for retinoid recycling (Lrat, Rpe65, and Rdh5) in RPE. Furthermore, they indicate circadian and light-dependent regulation of genes genetically associated with severe retinal diseases.

Visual phototransduction

RPE65

10.1167/iovs.18-24558

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Citations (12)

Nitric oxide synthase in the hypothalamic suprachiasmatic nucleus of rat: evidence from histochemistry, immunohistochemistry and Western blot; and colocalization with VIP

Brain Research (1995)

Stefan Reuss Karin Decker Lukas Röβeler Elisabeth Layes Andreas Schollmayer

Colocalization

Supraoptic nucleus

10.1016/0006-8993(95)00829-f

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Diabetic Goto Kakizaki rats as well as type 2 diabetic patients show a decreased diurnal serum melatonin level and an increased pancreatic melatonin‐receptor status

Journal of Pineal Research (2005)

Elmar Peschke Thomas Frese Erik Chankiewitz Dorothee Peschke U Preiß

There are functional inter-relationships between the beta cells of the endocrine pancreas and the pineal gland, where the synchronizing circadian molecule melatonin originates. The aim of this study was to elucidate a putative interaction between insulin and melatonin in diabetic patients and a diabetic rat model. We analyzed glucose, insulin, and melatonin levels of type 2 patients, as well as type 2 diabetic Goto Kakizaki (GK) rats by radioimmunoassay. Expression of pancreatic melatonin and pineal insulin receptors, as well as arylalkylamine-N-acetyltransferase (AANAT), was determined by real-time reverse transcriptase polymerase chain reaction (RT-PCR). The AANAT enzyme activity was measured in pineal homogenates. Diabetic patients showed a decrease in melatonin levels, while in the pancreas of GK rats an upregulation of the melatonin-receptor mRNA was determined. The pancreatic islets of GK rats showed expression of the mRNA for the pancreatic melatonin (MT1) receptor, which had previously been identified in rats and insulinoma (INS1) cells. Besides their presence in animal cells, the MT1-receptor transcript was also detected in human pancreas by RT-PCR. Whereas the rat pancreatic mRNA expression of the MT1-receptor was significantly increased, the activity of the pineal AANAT enzyme was reduced. The latter observation was in accordance with plasma melatonin levels. The insulin-receptor mRNA of the pineal gland was found to be reduced in GK rats. Our observations suggest a functional inter-relationship between melatonin and insulin, and may indicate a reduction of melatonin in the genesis of diabetes.

10.1111/j.1600-079x.2005.00287.x

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Citations (187)

Circadian gene expression patterns of melanopsin and pinopsin in the chick pineal gland

Biochemical and Biophysical Research Communications (2004)

Heike Holthues Lydia Engel Rainer Spessert Lutz Vollrath

Melanopsin

Darkness

Pinealocyte

10.1016/j.bbrc.2004.11.022

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Citations (35)

A differential role of CREB phosphorylation in cAMP-inducible gene expression in the rat pineal

Brain Research (2000)

Rainer Spessert Maria Rapp Holger Jastrow Nesrin Karabul Frank D. Blum

JUNB

CREB1

10.1016/s0006-8993(00)02185-5

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Citations (23)

Daily oscillation of gene expression in the retina is phase-advanced with respect to the pineal gland

Brain Research (2008)

Lin Bai Sybille Zimmer Oliver Rickes Nils H. Rohleder Heike Holthues

PER2

Pinealocyte

10.1016/j.brainres.2008.01.073

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Citations (32)

Evidence for a dysfunction and disease-promoting role of the circadian clock in the diabetic retina

Experimental Eye Research (2021)

Patrick Vancura Laura Oebel Simon K. B. Spohn Ute Frederiksen Kristina Schäfer

Pathophysiology

Pathogenesis

10.1016/j.exer.2021.108751

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Citations (10)

Lack of effect of oxytocin on the numbers of ?synaptic? ribbons, cyclic guanosine monophosphate and serotonin N-acetyltransferase activity in organ-cultured pineals of three strains of rats

Cell and Tissue Research (1993)

Stefan Reuss Eva Mattern Rainer Spessert Randolf Riemann Achim Weber

10.1007/bf00318752

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Citations (7)

The photoperiod entrains the molecular clock of the rat pineal

European Journal of Neuroscience (2005)

Lydia Engel Verena Lorenzkowski Christina Langer Nils H. Rohleder Rainer Spessert

Abstract The suprachiasmatic nucleus‐pineal system acts as a neuroendocrine transducer of seasonal changes in the photoperiod by regulating melatonin formation. In the present study, we have investigated the extent to which the photoperiod entrains the nonself‐cycling oscillator in the Sprague–Dawley rat pineal. For this purpose, the 24‐h expression of nine clock genes ( bmal1 , clock , per1 , per2 , per3 , cry1 , cry2 , dec1 and dec2 ) and the aa‐nat gene was monitored under light‐dark 8 : 16 and light‐dark 16 : 8 in the rat pineal by using real‐time RT‐PCR. The 24‐h pattern of the expression of only per1 , dec2 and aa‐nat genes was affected by photoperiod. In comparison with the short photoperiod, the duration of elevated expression under the long photoperiod was elongated for per1 and shortened for dec2 and aa‐nat . For each of the genes, photoperiod‐dependent variations partly persisted under constant darkness. Therefore, the pineal clockwork appears to memorize the photoperiod of prior entrained cycles. The findings of the present study indicate that the nonself‐cycling oscillator of the rat pineal is entrained by photoperiodic information and therefore that it participates in seasonal timekeeping.

PER1

PER2

Pinealocyte

Darkness

10.1111/j.1460-9568.2005.04040.x

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Citations (22)

Photoreceptor cells display a daily rhythm in the orphan receptor Esrrβ.

PubMed (2015)

Stefanie Kunst Tanja Wolloscheck Markus Grether Patricia Trunsch Uwe Wolfrum

Nuclear orphan receptors are critical for the development and long-term survival of photoreceptor cells. In the present study, the expression of the nuclear orphan receptor Esrrβ--a transcriptional regulator of energy metabolism that protects rod photoreceptors from dystrophy--was tested under daily regulation in the retina and photoreceptor cells.The daily transcript and protein amount profiles were recorded in preparations of the whole retina and microdissected photoreceptor cells using quantitative PCR (qPCR) and western blot analysis.Esrrβ displayed a daily rhythm with elevated values at night in the whole retina and enriched photoreceptor cells. Daily regulation of Esrrβ mRNA depended on light input but not on melatonin, and evoked a corresponding rhythm in the Esrrβ protein.The data presented in this study indicate that daily regulation of Esrrβ in photoreceptor cells may contribute to their adaptation to 24-h changes in metabolic demands.

Orphan receptor

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Citations (5)