Moreover, we recognized OR51E2 on protein level in a further pigment cell layer of the eye, the choroid

Moreover, we recognized OR51E2 on protein level in a further pigment cell layer of the eye, the choroid. is located between the choroids and the neural retina and represents a part of the blood-retina barrier (Rizzolo, 1997; Marmorstein, 2001). The RPE performs a variety of important functions that are essential for visual perception, such as light absorption, transepithelial transport, isomerization of all-trans to 11-cis retinal, secretion, and phagocytosis (Steinberg, 1985; Miller and Edelman, 1990; Bok, 1993; Stalmans and Himpens, 1997; Baehr et al., 2003; Besch et al., 2003; Strauss, 2005). Most of these functions are controlled by the intracellular Ca2+level, which, in turn, is regulated via G protein-coupled receptors (GPCR) (Wimmers et al., 2007). The genes coding for the odorant receptors (OR) were first demonstrated to be expressed in the olfactory epithelium of the rat, where they provide the elevation of intracellular calcium upon odor stimulation. These genes also symbolize the largest GPCR family in the human genome (Buck and Axel, 1991). OR expression is found in various human tissues outside the nose, such as the prostate, lung, liver, skin and testis (Feldmesser et al., 2006; Zhang et al., 2007; Flegel et al., 2013). The physiological roles of these ectopically expressed ORs are the subject of ongoing research. The few studies investigating their function show that the activation of human ORs leads to, for example , secretion processes or influences the cell proliferation such as OR51E2 in prostate cancer cells or in melanocytes (Spehr et al., 2003; Braun et al., 2007; Neuhaus et al., 2009; Veitinger et al., 2011; Sanz et al., 2014; Kang et al., 2015; Kim et al., 2015; Gelis Atazanavir sulfate (BMS-232632-05) et al., 2016; Kalbe et al., 2016b; Manteniotis et al., 2016b; Tsai et al., 2017; Weber et al., 2017). The various physiological functions depend on the tissue and respective OR. In the olfactory sensory neurons, ORs mediate a calcium influx, resulting in the generation of action potentials, which provide a crucial step that leads to olfactory perception (Nakamura and Precious metal, 1987). The activation of ectopically expressed ORs results, in most cases also, in an increase of the intracellular Ca2+level, but this is not always directly linked to the observed function. Interestingly, a recent transcriptome analysis revealed the cell specific expression of ORs in the human neural retina (Jovancevic et al., 2017b). In addition to the human neural retina, ORs were recognized in the human fetal RPE. Moreover, Ma and colleagues Atazanavir sulfate (BMS-232632-05) identified a mutation in an OR gene expressed in stem cell-derived human RPE cells that is associated with the autosomal dominant retinitis pigmentosa (Ma et al., 2015). However , subsequent commentaries on this study point out the limits of the data obtained by whole-exome sequencing (Zhang and Huang, 2015; Sharon et al., 2016). Early in their development, RPE cells undergo a terminal differentiation, resulting in a minimal proliferation capacity throughout normal life. However , RPE cell proliferation can be induced in disease conditions by a variety of growth factors (Stern and Temple, 2015). The activation of proliferation leads to a repair of RPE layer defects. However , an enhanced proliferation and migration could also be pathological and lead to proliferative vitreoretinopathy, a common cause of visual loss (Qiu et al., 2013). The purpose of the present study was to investigate the ectopic expression of ORs in the human RPE and the effects of OR activation on intracellular Ca2+level and physiological processes, such as migration and proliferation. == Materials and methods == == Cell culture == Primary retinal pigment epithelial cells from different human Rabbit Polyclonal to HEXIM1 donors (310 h postmortem) without any Atazanavir sulfate (BMS-232632-05) history of eye disease were obtained from the Eye Financial institution.