The shorter wavelengths of the visible light spectrum have been recently reported to induce a long-lasting hyperpigmentation but only in melano-competent individuals. Here, we provide evidence showing that OPN3 is the key sensor in melanocytes responsible for hyperpigmentation induced by the shorter wavelengths of visible light. The melanogenesis induced through OPN3 is calcium dependent and further activates CAMKII followed by CREB, extracellular signal-regulated kinase, and p38, leading to the phosphorylation of MITF and ultimately to the increase of the melanogenesis enzymes: tyrosinase and dopachrome tautomerase. Furthermore, blue light induces the formation of a protein complex that we showed to be formed by tyrosinase and dopachrome tautomerase. This multimeric tyrosinase/tyrosinase-related protein complex is mainly formed in dark-skinned melanocytes and induces a sustained tyrosinase activity, thus explaining the long-lasting hyperpigmentation that is observed only in skin type III and higher after blue light irradiation. OPN3 thus functions as the sensor for visible light pigmentation. OPN3 and the multimeric tyrosinase/tyrosinase-related protein complex induced after its activation appear as new potential targets for regulating melanogenesis but also to protect dark skins against blue light in physiological conditions and in pigmentary disorders.

UVA radiation is the most prevalent component of solar UV radiation; it deeply penetrates into the skin and induces profound alterations of the dermal connective tissue. In recent years, the detrimental effects of UVA radiation were more precisely demonstrated at cellular and molecular levels, using adequate methods to identify biological targets of UVA radiation and the resulting cascade impairment of cell functions and tissue degradation. In particular gene expression studies recently revealed that UVA radiation induces modulation of several genes confirming the high sensitivity of dermal fibroblasts to UVA radiation. The major visible damaging effects of UVA radiation only appear after years of exposure: it has been clearly evidenced that they are responsible for more or less early signs of photoageing and photocarcinogenesis. UVA radiation appears to play a key role in pigmented changes occurring with age, the major sign of skin photoaging in Asians. Skin susceptibility to photoaging alterations also depends on constitutive pigmentation. The skin sensitivity to UV light has been demonstrated to be linked to skin color type.

The sequence of events affecting skin morphogenesis occurring after a single exposure to UVB was investigated on a model of human skin reconstructed in vitro. The biologically efficient dose (BED) able to induce the early UVB-DNA damages such as pyrimidine dimers, sunburn cells, and apoptotic keratinocytes was determined as 50 mJ/cm2. The subsequent changes induced during a period of 14 days following irradiation were analyzed. Up to Day 3, an epidermal disorganization led to a parakeratotic epidermis characterized by nucleated horny layers, as well as the down regulation of major markers of keratinocyte differentiation such as keratin 10, loricrin, filaggrin, and the keratinocyte transglutaminase (type I). On the contrary, the expression of involucrin and spr1 seemed to be unaffected, indicating distinct responses to UVB of proteins involved in keratinocyte differentiation. A progressive regeneration of normal epidermal morphogenesis begins from Day 4 leading to the normalization of keratinocyte differentiation at Day 10 to 14. In parallel, epidermal proliferation was increased. Taken together, these findings show that in skin reconstructed in vitro, UVB exposure leads to major epidermal developmental changes characterized by (i) an early apoptotic process, (ii) a subsequent down-regulation of specific keratinocyte differentiation markers, and (iii) the recovery of both the early and delayed effects resulting in normal epidermal morphogenesis.

Galectin-7 is a ␤-galactoside binding protein specifically expressed in stratified epithelia and notably in epidermis, but barely detectable in epidermal tumors and absent from squamous carcinoma cell lines. Galectin-7 gene is an early transcriptional target of the tumor suppressor protein P53 [Polyak, K., Xia, Y., Zweier, J., Kinzler, K. & Vogelstein, B. (1997) Nature (London) 389, 300-305]. Because p53 transcriptional activity is increased by genotoxic stresses we have examined the possible effects of ultraviolet radiations (UVB) on galectin-7 expression in epidermal keratinocytes. The amounts of galectin-7 mRNA and protein are increased rapidly after UVB irradiation of epidermal keratinocytes. The increase of galectin-7 is parallel to P53 stabilization. UVB irradiation of skin reconstructed in vitro and of human skin ex vivo demonstrates that galectin-7 overexpression is associated with sunburn͞apoptotic keratinocytes. Transfection of a galectin-7 expression vector results in a significant increase in terminal deoxynucleotidyltransferase-mediated UTP end labeling-positive keratinocytes. The present findings demonstrate a keratinocyte-specific protein involved in the UVinduced apoptosis, an essential process in the maintenance of epidermal homeostasis.