Lutein and zeaxanthin isomers may attenuate photo-oxidative retinal damage via modulation of G protein-coupled receptors and growth factors in rats Kazim Sahin a, * , Hasan Gencoglu b , Fatih Akdemir c , Cemal Orhan a , Mehmet Tuzcu b , Nurhan Sahin a , Ismet Yilmaz d , Vijaya Juturu e a Department of Nutrition, Faculty of Veterinary Medicine, Firat University, Elazig, Turkey b Department of Biology, Faculty of Science, Firat University, Elazig, Turkey c Faculty of Fisheries, Inonu University, Malatya, Turkey d Department of Pharmacology, Faculty of Pharmacy, Inonu University, Malatya, Turkey e Research and Development, OmniActive Health Technologies Inc., Morristown, NJ, United States article info Article history: Received 14 May 2019 Accepted 7 June 2019 Available online xxx Keywords: Carotenoids GPCRs Lighteemitting diode Neurotrophins Photo-oxidation Retina abstract Background: Retina photoreceptor cells are specially adapted for functioning over comprehensive ambient light conditions. Lutein and Zeaxanthin isomers (L/Zi) can protect photoreceptor cells against excessive light degeneration. Efficacy of L/Zi has been assessed on some G protein-coupled receptors (GPCRs), transcription and neurotrophic factors in the retina of rats exposed to incremental intense light emitting diode (LED) illumination conditions. Methods: Forty-two male rats (age: 8 weeks) were randomly assigned to six treatment groups, 7 rats each. The rats with a 3x2 factorial design were kept under 3 intense light conditions (12hL/12hD, 16hL/ 8hD, 24hL/0hD) and received two levels of L/Zi (0 or 100 mg/kg BW) for two months. Increased nuclear factor-kappa B (NF-kB), glial fibrillary acid protein (GFAP), and decreased Rhodopsin (Rho), Rod arrestin (Sag), G Protein Subunit Alpha Transducin1 (Gnat1), neural cell adhesion molecule (NCAM), growth- associated protein-43 (GAP43), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), and heme oxygenase 1 (HO-1) were observed in 24 h light intensity adaptation followed by 16 h IL and 8 h D. Results: L/Zi administration significantly improved antioxidant capacity and retinal Rho, Rod-arrestin (Sag), Gnat1, NCAM, GAP43, BDNF, NGF, IGF1, Nrf2, and HO-1 levels. However, the levels of NF-kB and GFAP levels were decreased by administration of L/Zi. Conclusions: According to these results, L/Zi may be assumed as an adjunct therapy to prevent early photoreceptor cell degeneration and neutralize free radicals derived from oxidative stress. © 2019 Elsevier Inc. All rights reserved. 1. Introduction The retina is known for its high energy-consuming properties [1 ,2]. However, intense light exposure to the retina is included as reactive oxygen species (ROS) source, while the energy in a photon of light shifts the electron orbitals and breaks the direct bonds which contribute to the rapid free radical formation in- crease [3]. The retinal pigment epithelium is exposed to major degrees of blue light and high oxygen tension, which cause a high degree of oxidative stress. This oxidative damage is related to the age-related macular degeneration (AMD) pathogenesis [4]. AMD is clearly indicated to be associated with increased oxidative damage in many studies, with its several pathways [5]. The dis- ease acts on the macula at the center of the eye, resulting in central vision loss that significantly affects the patient's ability to view, watch, or drive, and it is the primary reason of permanent vision loss that affects millions of aged human populations glob- ally [6]. Epidemiological studies have been reported that the harmful blue light range is a risk factor for AMD due to accumu- lated ROS [7]. In addition, overexposure of light emitting diode (LED)-derived light is also known to be hazardous for the ocular regions, mainly the retina [8,9]. It is projected that the total * Corresponding author. F.A.C.N. Member of The Turkish Academy of Sciences, Professor of Nutrition Veterinary Faculty Firat University, 23119, Elazig, Turkey. E-mail addresses: nsahinkm@yahoo.com, ksahin@firat.edu.tr (K. Sahin). Contents lists available at ScienceDirect Biochemical and Biophysical Research Communications journal homepage: www.elsevier.com/locate/ybbrc https://doi.org/10.1016/j.bbrc.2019.06.032 0006-291X/© 2019 Elsevier Inc. All rights reserved. Biochemical and Biophysical Research Communications xxx (xxxx) xxx Please cite this article as: K. Sahin et al., Lutein and zeaxanthin isomers may attenuate photo-oxidative retinal damage via modulation of G protein-coupled receptors and growth factors in rats, Biochemical and Biophysical Research Communications, https://doi.org/10.1016/ j.bbrc.2019.06.032