6533b82efe1ef96bd1293c2e

RESEARCH PRODUCT

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

P. Michael IuvoneTanja WolloscheckPatrick VancuraKenkichi BabaRainer SpessertGianluca Tosini

subject

0301 basic medicineMalePhysiologyDopamineMice ObeseGene Expressionlcsh:MedicineBiochemistryAcyl-CoA DehydrogenaseMice0302 clinical medicineCatecholaminesEndocrinologyMedicine and Health SciencesAminesEnzyme Chemistrylcsh:ScienceBeta oxidationMice KnockoutMice Inbred C3HMultidisciplinaryOrganic CompoundsDopaminergicFatty AcidsNeurochemistryDiabetic retinopathyNeurotransmittersCircadian RhythmChemistryCircadian Oscillatorsmedicine.anatomical_structurePhysical SciencesFemaleAnatomyOxidation-Reductionmedicine.drugResearch Articlemedicine.medical_specialtyBiogenic AminesEndocrine DisordersOcular AnatomyBiologyRetinaEnzyme Regulation03 medical and health sciencesOcular SystemInternal medicinemedicineGeneticsDiabetes MellitusAnimalsPhotoreceptor CellsGene RegulationCircadian rhythmCarnitineACADMRetinaDiabetic RetinopathyCarnitine O-PalmitoyltransferaseReceptor Melatonin MT1Receptors Dopamine D4Organic Chemistrylcsh:RChemical CompoundsBiology and Life Sciencesmedicine.diseaseHormonesMice Inbred C57BLMetabolic pathwayDisease Models Animal030104 developmental biologyEndocrinologyMetabolismMicroscopy FluorescenceMetabolic DisordersEnzymologylcsh:Qsense organsEnergy MetabolismPhysiological ProcessesChronobiology030217 neurology & neurosurgeryNeuroscience

description

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.

10.1371/journal.pone.0164665http://europepmc.org/articles/PMC5058478?pdf=render