The patterns of melanosome distribution in keratinocytes of human skin as one determining factor of skin colour

Thong, Haw‐Yueh; Jee, Shiou‐Hwa; Sun, Cuojun; Boissy, Raymond E.

doi:10.1046/j.1365-2133.2003.05473.x

Cited by 168 publications

(150 citation statements)

References 17 publications

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“…[7] In black skin, melanosomes are large and remain as single organelles throughout the skin, while both forms are found in Asian skin. [8] Over a hundred genes are thought to play a role in melanin synthesis and melanocyte function; however, only 11 have been confirmed as key determinants of normal skin pigment variation through genome-wide association studies to date, [9] with some genes linked exclusively to either inter-or intra-population variation. Fewer genes have been implicated in determining hair and eye colour, with the melanocortin-1 receptor (MC1R) shown to be the 'red hair' gene [10] and OCA2 the 'brown eyes' gene.…”

Section: Biology Of Pigmentationmentioning

confidence: 99%

Biology and genetics of oculocutaneous albinism and vitiligo – common pigmentation disorders in southern Africa

et al. 2013

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The primary pigment that determines human skin, hair and eye colour is melanin, which is synthesised by melanocytes. Melanin protects the skin from ultraviolet (UV) radiation and there is an inverse correlation between the degree of constitutive pigmentation and the risk of sun-induced skin cancers. Besides the life-threatening cancer risk, loss of pigmentation results in premature aging, compromised cutaneous immunity and significant emotional distress to affected individuals. [1][2][3] During embryonic development, melanocyte precursors that arise from the neural crest populate several areas including the interfollicular epidermis and hair follicle bulge in the skin; the uveal tract of the eye; and the stria vascularis, vestibular apparatus and endolymphatic sac of the ear. The development of melanocytes is tightly regulated at the genetic level by a number of genes that control proliferation, survival and migration of precursor cells to the various sites of the body and their differentiation into active melanocytes. A key regulator of this process is the microphthalmia transcription factor (MITF), which has been dubbed the 'master regulator' of the melanocyte, capable of modulating expression of several melanocytespecific proteins.[4] MITF mutations result in Waardenburg syndrome type II.[5] Once the melanocyte has differentiated, MITF regulates expression of genes in response to UV exposure, facilitating the tanning response.Melanocytes produce two forms of melanin, black-brown eumelanin and red-yellow pheomelanin. Skin and hair colour Corresponding author: P Manga (prashiela.manga@nyumc.org)Pigmentation disorders span the genetic spectrum from single-gene autosomal recessive disorders such as oculocutaneous albinism (OCA), the autosomal dominant disorder piebaldism to X-linked ocular albinism and multifactorial vitiligo. OCA connotes a group of disorders that result in hypopigmented skin due to decreased melanin production in melanocytes and loss of visual acuity. There are four non-syndromic forms, OCA1-4, which are classified based on the gene that is mutated (tyrosinase, OCA2, tyrosinase-related protein 1 and SLC45A2, respectively). Despite the fact that multiple genes account for the various forms of OCA, the phenotypes of all four forms result from disruption in the maturation and trafficking of the enzyme tyrosinase. OCA2 is the most prevalent autosomal recessive disorder among southern African blacks, affecting 1/3 900 individuals; while OCA3, although rare, is most prevalent in southern Africa. Another common pigmentation disorder in southern Africa is vitiligo, which affects 1 -2% of people worldwide. Vitiligo is a complex, acquired disorder in which melanocytes are destroyed due to an autoimmune response. The aetiology underlying this disorder is poorly understood, although recent genetic association studies have begun to shed light on the contributing factors. Pigmentation disorders have significant psychosocial implications and co-morbidities, yet therapies are still lacking. Recent progress in...

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Section: Biology Of Pigmentationmentioning

confidence: 99%

Biology and genetics of oculocutaneous albinism and vitiligo – common pigmentation disorders in southern Africa

et al. 2013

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“…Although the spread of melanin through the simulated epidermis differed due to the differences in the initial skin models, the final prediction from the two experiments were similar overall ( Table 2). The melanosome diameters predicted from the two experiments were identical, although they were greater than expected these skin types [12][13][14][15][16].…”

Section: Minimisation Procedures -Melanin Adjustmentmentioning

confidence: 59%

“…The layer representing the living epidermis in Meglinski and Matcher's work was divided into two layers in the new programme in order to facilitate differences in melanin properties (Table 1). Estimations of representative melanosome concentrations and sizes were based upon an analysis of the literature [11][12][13][14][15][16]. [14].…”

Section: Skin Modelmentioning

confidence: 99%

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A new Monte Carlo program for simulating light transport through Port Wine Stain skin

2013

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A new Monte Carlo programme is presented for simulating light transport through clinically normal skin and skin that has Port Wine Stains (PWS) vessels. The program consists of an eight layer mathematical skin model constructed from optical coefficients described previously.A simulation including diffuse illumination at the surface and subsequent light transport through the model is carried out using a Radiative Transfer Theory (RTT) ray-tracing technique. Total reflectance values over 39 wavelengths are scored by the addition of simulated light returning to the surface within a specified region and surface reflections (calculated using Fresnel's equations). These reflectance values are compared to measurements from individual participants and characteristics of the model are adjusted until adequate agreement is produced between simulated and measured skin reflectance curves.The absorption and scattering coefficients of the epidermis are adjusted through changes in the simulated concentrations and mean diameters of epidermal melanosomes to reproduce non-lesional skin colour. Pseudo-cylindrical horizontal vessels are added to the skin model and their simulated mean depths, diameters and number densities are adjusted to reproduce measured PWS skin colour.Accurate reproductions of colour measurement data are produced by the program, resulting in realistic predictions of melanin and PWS blood vessel parameters. Using a modest personal computer, the simulation currently requires an average of five and a half days to complete.

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“…However, contributions from melanin being produced and stored and leading to tumors in different melanocytic cell types in fish (melanophores and macromelanophores) (4, 16) or from differences in skin structure or lowered DNA repair compared with humans also may be important, so direct comparison between the two cases is difficult. The relative resistance of darker-skinned humans to UV induction of melanoma compared with lighter-skinned humans is also complex but likely involves contributions from increases in melanosome size leading to lower fluxes of oxidants from larger melanin aggregates in darker skins (28), increased melanosome͞melanin levels in upper epidermal layers protecting underlying melanocytes (29,30), and the lack of pheomelanin, which is a more powerful photosensitizer than eumelanin (31).…”

Section: Resultsmentioning

confidence: 99%

UV causation of melanoma in Xiphophorus is dominated by melanin photosensitized oxidant production

Wood¹,

Berwick²,

Ley

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

109

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Controversy continues both as to which wavelengths of sunlight cause melanoma and the mechanisms by which these different wavelengths act. Direct absorption of UVB by DNA is central in albino animal models, but melanin-pigmented models have shown major contributions by wavelengths longer than UVB that are thought to be mediated by photosensitized oxidant production. The only model for which the action spectrum of melanoma causation is known is a genetically melanoma-susceptible specific cross of Xiphophorus fish. We used electron paramagnetic resonance to quantitatively detect the UV induction of reactive melanin radicals in situ in the melanin-containing cells in the skin of this model and derived the action spectrum for melanin-photosensitized oxidant production (⌽ ox). This action spectrum was identical to that for melanoma induction (⌽ mel). These results confirm the hypothesis that melanin-photosensitized radical production is the major causative step of melanoma in this model and demonstrate that the wavelengths and mechanisms of melanoma causation in different models are dependent on the presence of melanin. This approach should be applicable to humans, thus providing an accurate surrogate for ⌽ mel for prevention studies.action spectrum ͉ free radical C utaneous malignant melanoma incidence continues to increase (1), yet prevention strategies are hindered by a lack of knowledge of which wavelengths of sunlight cause melanoma, and the mechanisms by which these different wavelengths cause melanoma are not understood. Although nonmelanoma skin cancers are predominantly caused by UVB wavelengths, melanoma causation has efficiently been observed by wavelengths longer than UVB, such as UVA, with this observation supported by both experimental animal (2-4) and human epidemiological evidence (5-7). However, the role of UVA in melanoma causation still remains controversial (8, 9). Similarly, there is controversy over the mechanisms by which these different wavelengths act. The prevailing view is that UVA leads to DNA photooxidation, with melanin thought to be the important photosensitizer when present, whereas UVB leads to pyrimidine dimer formation through direct absorption by DNA (6, 10). The relative importance of UVB and UVA in these processes is, however, currently under scrutiny, because some have found that UVA appears able to produce pyrimidine dimers in cultured cells (11,12), whereas melanin can act as an efficient UVB sensitizer in vivo (13), and so these questions need further investigation.The question of which wavelengths cause a biological effect, in this case melanoma, is best evaluated through measuring the wavelength dependence of that effect to generate its action spectrum (14). Although melanoma has been observed in many species (15), there is only one model in which the action spectrum of melanoma causation has been determined, namely select interspecies crosses of Xiphophorus fish (4, 16). Despite the phylogenetic distance between Xiphophorus and humans, and the differences in skin structure...

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The patterns of melanosome distribution in keratinocytes of human skin as one determining factor of skin colour

Abstract: The present data indicate that there may be a size gradient of melanosomes encompassing the global complexion coloration and that the melanosome distribution in keratinocytes of Asian skin is intermediate between that in light Caucasian and dark African/American skin.

Cited by 168 publications

References 17 publications

Biology and genetics of oculocutaneous albinism and vitiligo – common pigmentation disorders in southern Africa

Biology and genetics of oculocutaneous albinism and vitiligo – common pigmentation disorders in southern Africa

A new Monte Carlo program for simulating light transport through Port Wine Stain skin

UV causation of melanoma in Xiphophorus is dominated by melanin photosensitized oxidant production

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