Illuminating insights into opsin 3 function in the skin
Introduction
Life on earth depends on sunlight—it is a sine qua non condition for human survival. Because sunlight can, arguably, only penetrate skin-deep, its complex effects must be mediated by those organs that light can reach under physiological conditions—our eyes and skin. How light evokes responses in retinal cells to mediate vision has been investigated for many decades (Hisatomi and Tokunaga, 2002; Shichida and Imai, 1998). In addition to rods and cones that mediate vision, the retina also contains cells responsible for the light-dependent entrainment of circadian rhythm (Berson, 2002; Provencio et al., 2000) and other visual and non-visual functions (Berson, 2007; Panda et al., 2002; Sikka et al., 2014). These light-induced responses in the retina are mediated by opsins, a family of light-sensitive G-protein coupled receptors (GPCRs) that covalently bind a retinal chromophore.
Skin, the largest organ of our body, is also constantly exposed to sunlight. While specific skin responses to visible light remain a matter of debate, exposure to solar ultraviolet (UV) radiation has a plethora of short- and long-term effects on skin: DNA damage, oxidative stress, increased pigmentation and photoaging (Cui et al., 2007; Holick, 2008; Honigsmann, 2002; Kiyonaka et al., 2013). Solar UV radiation is comprised of ~95% long wavelength UVA and ~5% short wavelength UVB, each activating distinct signaling pathways in the skin. UVB induces DNA damage, triggering the increase in pigmentation within many hours to days (Cui et al., 2007), while physiological doses of UVA trigger a retinal-dependent G-protein coupled signaling pathway causing immediate pigment darkening via activation of an unknown receptor (Bellono et al., 2013, 2014; Wicks et al., 2011). The retinal-dependence and involvement of G-proteins in the UVA pathway makes it tempting to speculate that the skin, similar to the eye, uses retinal-bound opsin receptors to respond to light. Here we review recent findings related to the expression and function of opsins in skin cells, particularly focusing on elucidating the elusive roles of opsin 3 (OPN3).
Section snippets
Visual phototransduction
Retinal cells respond to different wavelengths of light via activation of opsins with distinct spectral sensitivities [reviewed in (Terakita, 2005)]. An opsin's light sensing ability is due to its interaction with a light-sensitive chromophore (Pitt et al., 1955). In an inactive form, the opsin apoprotein forms a covalent bond with an endogenously-produced, vitamin A-derived chromophore, most often 11-cis retinal in mammals. Absorption of a photon by the bound retinal induces its isomerization
Skin phototransduction
Human skin is structured in layers: the uppermost layer, the epidermis, is comprised of keratinocytes surrounding a single basal layer of melanin-producing melanocytes; the dermis comprises a middle fibrous layer; the subcutis is a cushioning layer upon which the epidermis and dermis rest (Simpson et al., 2011). How deep solar UV radiation penetrates the skin layers depends on its energy; UVA penetrates through both the epidermis and dermis, whereas UVB is primarily confined to the epidermis (
OPN3 properties and function in skin
OPN3 was first discovered in 1999 in the mouse brain (Blackshaw and Snyder, 1999). Shortly after, human OPN3 was found to be expressed in a wide array of peripheral tissues including the brain, placenta, retina, liver, heart, lung, skeletal muscle, pancreas (Halford et al., 2001), and skin (Haltaufderhyde et al., 2015), affording the colloquial name panopsin. Paradoxically, OPN3 is equipped to be light-sensitive (see below), yet it is expressed in an array of tissues not exposed to light under
Conclusions and future directions
The last decade of research brought skin photodetection and photosensitivity into the spotlight. Although the connection between the ability of our eyes and skin to detect light might seem obvious because light is a physiological stimulus for both, it was the discovery that melanopsin (subsequently named OPN4) is expressed in photosensitive dermal melanophores of Xenopus laevis (Provencio et al., 1998), that brought opsins and dermal photodetection together. The unexpected finding that visual
Methods
Animals and immunohistochemistry. All animal care and procedures were performed in accordance with the Brown University Institutional Animal Care and Use Committee as in compliance with the National Institutes of Health guide for the care and use of laboratory animals. Animals were housed socially with ad libitum access to food and water in a light- (12 h light/dark cycle) and temperature-controlled (21.5–22.5 °C) facility. OPN3−/− mice (Buhr et al., 2015) were a generous gift from Dr. K.-W.
Declaration of competing interest
The authors declare no conflicts of interest.
Acknowledgements
We thank Dr. K.-W. Yau of Johns Hopkins University for generously providing the OPN3−/− mouse model (Buhr et al., 2015), used as a control for the OPN3-mCherry immunostaining. We also thank present and former members of the Oancea lab, especially Dr. Rana Ozdeslik, for insightful discussions and feedback during the development of the OPN3 project. The research in the laboratory of E.O. as related to this review was supported by the National Institute of Arthritis and Musculoskeletal and Skin
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