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

• Type of Material: Article
• Authors: Patrick Vancura, Johannes Gutenberg University; Tanja Wolloscheck, Johannes Gutenberg University; Kenkichi Baba, Morehouse School of Medicine; Gianluca Tosini, Emory University; Paul Iuvone, Emory University; Rainer Spessert, Johannes Gutenberg University
• Language: English
• Date: 2016-10-11
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2016 Vancura et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pone.0164665
• Title of Journal or Parent Work: PLoS ONE
• ISSN: 1932-6203
• Volume: 11
• Issue: 10
• Start Page: e0164665
• End Page: e0164665
• Grant/Funding Information: This research was funded in part by grants from the National Institutes of Health: R01EY004864 to PMI, R01EY0222 to GT,P30EY006360 to PMI, and an unrestricted departmental grant from Research to Prevent Blindness to PMI.
• Keywords: Chronobiology; RABBIT RETINA; Enzyme regulation; EXPRESSION; BETA-OXIDATION; ADENYLYL-CYCLASE; Retina; Diabetes mellitus; CLOCK GENES; Science & Technology; CARNITINE PALMITOYLTRANSFERASE-I; Energy metabolism; MOUSE RETINA; COACTIVATOR PGC-1; Circadian oscillators; Gene regulation; MAMMALIAN RETINA; Multidisciplinary Sciences; Dopamine
• Research Categories: Biology, Physiology; Health Sciences, Opthamology

Abstract

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.