Transcriptional analysis of rat photoreceptor cells reveals daily regulation of genes important for visual signaling and light damage susceptibility

Kunst, Stefanie; Wolloscheck, Tanja; Hölter, Philip; Wengert, Alexander; Grether, Markus; Sticht, Carsten; Weyer, Veronika; Wolfrum, Uwe; Spessert, Rainer

doi:10.1111/jnc.12089

Cited by 9 publications

(16 citation statements)

References 60 publications

(65 reference statements)

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“…Using the RNeasy Micro Kit (Qiagen, Hilden, Germany) RNA was extracted from the tissue samples as described [ 35 ]. The amount of extracted RNA was determined by measuring the optical density at 260 and 280 nm.…”

Section: Methodsmentioning

confidence: 99%

Circadian and Dopaminergic Regulation of Fatty Acid Oxidation Pathway Genes in Retina and Photoreceptor Cells

et al. 2016

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The energy metabolism of the retina might comply with daily changes in energy demand and is impaired in diabetic retinopathy—one of the most common causes of blindness in Europe and the USA. The aim of this study was to investigate putative adaptation of energy metabolism in healthy and diabetic retina. Hence expression analysis of metabolic pathway genes was performed using quantitative polymerase chain reaction, semi-quantitative western blot and immunohistochemistry. Transcriptional profiling of key enzymes of energy metabolism identified transcripts of mitochondrial fatty acid β-oxidation enzymes, i.e. carnitine palmitoyltransferase-1α (Cpt-1α) and medium chain acyl-CoA dehydrogenase (Acadm) to display daily rhythms with peak values during daytime in preparations of the whole retina and microdissected photoreceptors. The cycling of both enzymes persisted in constant darkness, was dampened in mice deficient for dopamine D4 (D4) receptors and was altered in db/db mice—a model of diabetic retinopathy. The data of the present study are consistent with circadian clock-dependent and dopaminergic regulation of fatty acid oxidation in retina and its putative disturbance in diabetic retina.

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Section: Methodsmentioning

confidence: 99%

Circadian and Dopaminergic Regulation of Fatty Acid Oxidation Pathway Genes in Retina and Photoreceptor Cells

et al. 2016

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“…Using the RNeasy Micro kit (Qiagen, Hilden, Germany), RNA was extracted from the tissue samples as described. 33 The amount of extracted RNA was determined by measuring the optical density at 260 and 280 nm. Subsequently, single-stranded cDNA was synthesized by using the Verso cDNA Kit (Abgene, Hamburg, Germany), following the manufacturer's instructions.…”

Section: Methodsmentioning

confidence: 99%

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

Vancura

Csicsely

Leiser

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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PurposeThe aim of the present study was to identify candidate genes for mediating daily adjustment of vision.MethodsGenes 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.ResultsPhotoreceptors 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.ConclusionsThe 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.

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“…Using the RNeasy Micro Kit (Qiagen, Hilden, Germany) RNA was extracted from the tissue samples as described previously [ 26 ]. Subsequently first stranded cDNA was synthesized using the Verso cDNA Kit (Abgene, Hamburg, Germany), following the manufacturer’s instructions.…”

Section: Methodsmentioning

confidence: 99%

Gnaz couples the circadian and dopaminergic system to G protein-mediated signaling in mouse photoreceptors

et al. 2017

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The mammalian retina harbors a circadian clockwork that regulates vision and promotes healthiness of retinal neurons, mainly through directing the rhythmic release of the neurohormones dopamine—acting on dopamine D4 receptors—and melatonin—acting on MT1 and MT2 receptors. The gene Gnaz—a unique Gi/o subfamily member—was seen in the present study to be expressed in photoreceptors where its protein product Gαz shows a daily rhythm in its subcellular localization. Apart from subcellular localization, Gnaz displays a daily rhythm in expression—with peak values at night—in preparations of the whole retina, microdissected photoreceptors and photoreceptor-related pinealocytes. In retina, Gnaz rhythmicity was observed to persist under constant darkness and to be abolished in retina deficient for Clock or dopamine D4 receptors. Furthermore, circadian regulation of Gnaz was disturbed in the db/db mouse, a model of diabetic retinopathy. The data of the present study suggest that Gnaz links the circadian clockwork—via dopamine acting on D4 receptors—to G protein-mediated signaling in intact but not diabetic retina.

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Transcriptional analysis of rat photoreceptor cells reveals daily regulation of genes important for visual signaling and light damage susceptibility

Cited by 9 publications

References 60 publications

Circadian and Dopaminergic Regulation of Fatty Acid Oxidation Pathway Genes in Retina and Photoreceptor Cells

Circadian and Dopaminergic Regulation of Fatty Acid Oxidation Pathway Genes in Retina and Photoreceptor Cells

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

Gnaz couples the circadian and dopaminergic system to G protein-mediated signaling in mouse photoreceptors

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