Melanopsin as the UVA photoreceptor and its relationship with pigmentation, DNA repair, biological clock and components of the HPA axis: a novel pharmacological target?

Abstract

The mammalian photosensitive system committed to non-image forming processes has been well characterized in the eyes. The components of this system are the opsins, biological sensors of light. Opsins are also present in the skin cells, but the biological processes they regulate are largely unknown. Recent evidence resulting from our work and others indicate the role of these sensors in the regulation of pigmentation by light and ultraviolet radiation and in keratinocyte differentiation. Skin cells also possess a complex system of temporal control, which is capable of "marking time" thus providing the cutaneous cells with time information. This system is composed of clock genes, which time key processes such as proliferation, DNA repair, among others. Our group is a world leader in both research fields. In addition, the skin is by itself a complex neuroendocrine system able to synthesize and secrete a variety of chemical messengers identical to the ones produced by the central neuroendocrine axis. It has been demonstrated that UVB and UVA radiation directly stimulate the skin to synthesize several messengers which exert local as well as systemic actions. Till now, the mechanism of UVA has been poorly investigated and the receptor mediating these effects is still unknown. We have demonstrated that melanopsin is a UVA sensor, therefore we hypothesize that UVA excites skin melanopsin, which triggers a signaling cascade culminating with pigmentation processes, DNA repair, modulation of the biological clock and local and central synthesis of hormones. To answer these questions, we will expose wild type and melanopsin knockout mice to UVA and assess pigmentation, DNA repair, gene and protein quantification of clock genes, hormone quantification and total sequencing of mRNA. Through the use of animal models and advanced techniques of molecular biology we will establish the role of melanopsin in the skin, opening the perspective of a novel pharmacological target. (AU)