Melanocytes Sense Blue Light and Regulate Pigmentation through Opsin-3

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.