1.1 Overview
3
RPE cells are optic cup-derived cells, and form the pigmented layer in the development of the retina. Melanin pigments in the RPE cells are responsible for absorbing
light. Unlike cutaneous melanins, these optic cup-originated melanins are actively
formed only before the completion of the differentiation to the RPE cells, and then
show slow turnover (i.e. a dynamic equilibrium between production and decomposition). While the skin and the hair colors depend on transportation of melanins from the
melanocytes to the outer layer of the epidermis, the RPE cells directly use the intracellularly synthesized melanins for their light absorption [6]. Aside from melanins
synthesized in pigment cells, there are also melanin-like pigments in the neurons
located at the substantia nigra and the locus coeruleus of the brain. These pigments
are called neuromelanins and their biological effects, such as binding of Parkinson’s
disease-related heavy metal ions and molecules (e.g. methylphenylpyridine: MPP+),
have been pointed out [7, 8].
1.1.3 The Significance and the Scope of Melanin Study
Melanin study covers wide branches of science. From the biodiversity point of
view, melanin-based pigmentation is an important biology topic as it contributes
to the various visual phenotypes. Understanding the origin of the visual phenotypes requires connecting the genetics of the color polymorphism with knowledge of the body coloration. Dermatologists have been struggling to explore the
etiology/pathogenesis and the prevention/treatment of melanin- or melanocyteassociated diseases including pigmentary disorders, such as oculocutaneous albinism
(OCA) and vitiligo vulgaris, and the malignant tumor of melanocytes, namely
melanoma.
As the main color-determining factors are the amount of melanin and its composition (the ratio of eumelanin/pheomelanin), the lesions in pigmentary disorders display
an irregular amount of melanin production, melanin transportation, and number of
melanocytes. OCA is a congenital disorder characterized by dysfunction of melanin
production, and designated as an intractable disease in Japan. Vitiligo is an idiopathic
leukoderma resulting from loss of melanocytes, which can cause a widespread depigmentation for non-segmental cases. Although the etiology of vitiligo is still controversial, irregularly sensitized immune responses are widely accepted as an important
factor contributing to the initiation and the progression of vitiligo [9].
Aside from pigmentary disorders, controlling the biosynthesis and the transportation of cutaneous melanins has been a longtime theme in cosmetic sciences. To
achieve this artificial control of pigmentation, a multi-disciplinary investigation of
melanin formation, involving chemistry, biology, and dermatology, is necessary.
Melanoma is a notorious cancer which has poor prognoses. As surgical resection of
metastatic and invasive melanoma is poorly effective, chemotherapeutic agents have
been used for the treatment of advanced melanoma. Although alkylating agents have a
long history of application to chemotherapy, they are still not satisfactorily successful
because of their limited response rates (efficacies) and their severe adverse effects.
3
RPE cells are optic cup-derived cells, and form the pigmented layer in the development of the retina. Melanin pigments in the RPE cells are responsible for absorbing
light. Unlike cutaneous melanins, these optic cup-originated melanins are actively
formed only before the completion of the differentiation to the RPE cells, and then
show slow turnover (i.e. a dynamic equilibrium between production and decomposition). While the skin and the hair colors depend on transportation of melanins from the
melanocytes to the outer layer of the epidermis, the RPE cells directly use the intracellularly synthesized melanins for their light absorption [6]. Aside from melanins
synthesized in pigment cells, there are also melanin-like pigments in the neurons
located at the substantia nigra and the locus coeruleus of the brain. These pigments
are called neuromelanins and their biological effects, such as binding of Parkinson’s
disease-related heavy metal ions and molecules (e.g. methylphenylpyridine: MPP+),
have been pointed out [7, 8].
1.1.3 The Significance and the Scope of Melanin Study
Melanin study covers wide branches of science. From the biodiversity point of
view, melanin-based pigmentation is an important biology topic as it contributes
to the various visual phenotypes. Understanding the origin of the visual phenotypes requires connecting the genetics of the color polymorphism with knowledge of the body coloration. Dermatologists have been struggling to explore the
etiology/pathogenesis and the prevention/treatment of melanin- or melanocyteassociated diseases including pigmentary disorders, such as oculocutaneous albinism
(OCA) and vitiligo vulgaris, and the malignant tumor of melanocytes, namely
melanoma.
As the main color-determining factors are the amount of melanin and its composition (the ratio of eumelanin/pheomelanin), the lesions in pigmentary disorders display
an irregular amount of melanin production, melanin transportation, and number of
melanocytes. OCA is a congenital disorder characterized by dysfunction of melanin
production, and designated as an intractable disease in Japan. Vitiligo is an idiopathic
leukoderma resulting from loss of melanocytes, which can cause a widespread depigmentation for non-segmental cases. Although the etiology of vitiligo is still controversial, irregularly sensitized immune responses are widely accepted as an important
factor contributing to the initiation and the progression of vitiligo [9].
Aside from pigmentary disorders, controlling the biosynthesis and the transportation of cutaneous melanins has been a longtime theme in cosmetic sciences. To
achieve this artificial control of pigmentation, a multi-disciplinary investigation of
melanin formation, involving chemistry, biology, and dermatology, is necessary.
Melanoma is a notorious cancer which has poor prognoses. As surgical resection of
metastatic and invasive melanoma is poorly effective, chemotherapeutic agents have
been used for the treatment of advanced melanoma. Although alkylating agents have a
long history of application to chemotherapy, they are still not satisfactorily successful
because of their limited response rates (efficacies) and their severe adverse effects.