As humans we are social beings where uneven or asymmetric pigmentation on the face and other areas of the body can cause lowered self-esteem, depression, problems with social status and reduced productivity in the workplace (Balkrishnan et al., 2006, Int J Dermatol 45:111-5). Hyperpigmentation of the skin is a common condition for which many individuals seek corrective treatment. It is the result of increased cutaneous melanin, sometimes asymmetrically in a spot or covering particular regions of skin; in other cases with bilateral symmetry. This can be caused by increased melanin synthesis and transfer to keratinocytes; a greater number of melanocytes; and in some cases by melanophages, melanin-containing macrophages that accumulate melanin through phagocytosis. Hyperpigmented regions are brown to blue-grey. There are many causes of hyperpigmentation, some of the most common being melasma, post-inflammatory hyperpigmentation (PIH) and solar lentigenes (liver spots).
Melanocytes are the pigment producing cells of the skin. Melanins, the chief pigments, are synthesized by a group of enzymes located in small cellular bodies known as melanosomes in the cytoplasm of melanocytes. Melanocytes are located in the basal layer of the epidermis in close contact with keratinocytes to which they donate melanin. On the average, humans have about the same number of melanocytes per mm2 of skin regardless of ethnic background. Each melanocyte is associated with about 36 keratinocytes in an “epidermal-melanin unit”. Normally it is not the number of melanocytes but the activity of the melanocytes, including synthesis of melanin and its transfer to keratinocytes that determines our actual skin color and intensity. Melanosomes laden with melanin are transferred from melanocytes to surrounding keratinocytes, the most abundant cells of the skin, imparting coloration and sun protection to the skin (FIG. 1).
Melanosome transfer to keratinocytes is a unique biological process involving organelle donation from one cell to another and is a crucial step in skin pigmentation. Individuals with defects in this process can have markedly reduced skin melanin content. The process involves the attachment of melanocytes to keratinocytes; transfer of melanosomes into keratinocytes; and, in skin, trafficking to the supranuclear area of the keratinocyte. There is growing information on melanocyte-keratinocyte transfer regarding cell biology, cytokine and hormonal signaling pathways and the role of peptides and proteins (Scott et al., 2007, Exp Cell Res 313:3840-50; Scott et al., 2008, J Invest Dermatol 128:151-61; Scott, 2012, J Invest Dermatol 132(4):1073-4; Singh et al., 2012, J Cell Sci 125(Pt 18):4306-19). However, there remains a need in the art for compositions and methods for treating and preventing hyperpigmentation. The present invention satisfies this unmet need.