Abstract
The odorant receptor 51E2 (OR51E2), which is well-characterized in prostate cancer cells and epidermal pigment cells, was identified for the first time as the most highly expressed OR in human fetal and adult retinal pigment epithelial (RPE) cells. Immunofluorescence staining and Western blot analysis revealed OR51E2 localization throughout the cytosol and in the plasma membrane. Additionally, immunohistochemical staining of diverse layers of the eye showed that the expression of OR51E2 is restricted to the pigment cells of the RPE and choroid. The results of Ca2+-imaging experiments demonstrate that activation of OR51E2 triggers a Ca2+ dependent signal pathway in RPE cells. Downstream signaling of OR51E2 involves the activation of adenylyl cyclase, ERK1/2 and AKT. The activity of these protein kinases likely accounts for the demonstrated increase in the migration and proliferation of RPE cells upon stimulation with the OR51E2 ligand β-ionone. These findings suggest that OR51E2 is involved in the regulation of RPE cell growth. Thus, OR51E2 represents a potential target for the treatment of proliferative disorders.
Highlights
The retinal pigment epithelium (RPE), a monolayer of pigmented polarized cells, is located between the choroids and the neural retina and represents a part of the blood-retina barrier (Rizzolo, 1997; Marmorstein, 2001)
Apart from the expression level, odorant receptor 51E2 (OR51E2) represent an interesting target for the characterization of an odorant receptors (OR) in retinal pigment epithelial (RPE) cells because it is one of the few human ORs for which ligands (β-ionone, short chain fatty acids and androstenone derivatives) have been identified (Neuhaus et al, 2009; Saito et al, 2009)
We focused on investigating the function of OR51E2 in primary RPE cells
Summary
The retinal pigment epithelium (RPE), a monolayer of pigmented polarized cells, 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 proteincoupled receptors (GPCR) (Wimmers et al, 2007). An enhanced proliferation and migration could be pathological and lead to proliferative vitreoretinopathy, a common cause of visual loss (Qiu et al, 2013)
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