Vitiligo pp 103-113 | Cite as

Extra-Cutaneous Melanocytes

  • Tag S. Anbar
  • Rehab A. Hegazy
  • Suzan Shalaby


Besides their being in the skin, melanin and melanocytes are detected in the eye, stria vascularis of the cochlea in the ear, leptomeninges, substantia nigra, and locus coeruleus of the brain, heart, and lungs. In vitiligo, although melanocyte loss has been recognized as being mainly restricted to the skin, extra-cutaneous melanocyte involvement and subsequent extra-cutaneous site alterations have been detected. The knowledge of extra-cutaneous involvement may point toward considering vitiligo as a systemic disorder rather than just a cosmetic problem. Still, no clear guidelines on who deserve screening of their extra-cutaneous melanocyte sites in cases of vitiligo exist, an aim yearning to be fulfilled.


  1. 1.
    Tolleson WH. Human melanocyte biology, toxicology, and pathology. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2005;23(2):105–61.. Review.CrossRefGoogle Scholar
  2. 2.
    Tachibana M. Sound needs sound melanocytes to be heard. Pigment Cell Res. 1999;12:344–54.CrossRefGoogle Scholar
  3. 3.
    Goldgeier MH, Klein LE, Klein-Angerer S, et al. The distribution of melanocytes in the leptomeninges of the human brain. J Invest Dermatol. 1984;82(3):235–8.CrossRefGoogle Scholar
  4. 4.
    Zecca L, Tampellini D, Gatti A, et al. The neuromelanin of human substantia nigra and its interaction with metals. J Neural Transm. 2002;109:663–72.CrossRefGoogle Scholar
  5. 5.
    Brito FC, Kos L. Timeline and distribution of melanocyte precursors in the mouse heart. Pigment Cell Melanoma Res. 2008;21:464–70.CrossRefGoogle Scholar
  6. 6.
    Yajima I, Larue L. The location of heart melanocytes is specified and the level of pigmentation in the heart may correlate with coat color. Pigment Cell Melanoma Res. 2008;21:471–6.CrossRefGoogle Scholar
  7. 7.
    Ferrans VJ, Yu ZX, Nelson WK, et al. Lymphangioleiomyomatosis (LAM). a review of clinical and morphological features. J Nippon Med Sch. 2000;67:311–29.CrossRefGoogle Scholar
  8. 8.
    Randhawa M, Huff T, Valencia JC, et al. Evidence for the ectopic synthesis of melanin in human adipose tissue. FASEB J. 2009;23:835.CrossRefGoogle Scholar
  9. 9.
    Brenner M, Vincent J. Hearing. “What are melanocytes really doing all day long…? : from the viewpoint of a keratinocyte: melanocytes – cells with a secret identity and incomparable abilities.”. Exp Dermatol. 2009;18(9):799–819.CrossRefGoogle Scholar
  10. 10.
    Mills MD, Albert DM. Ocular and otic findings in vitiligo. In: Hann SK, Nordlund JJ, editors. Vitiligo: a monograph on the basic and clinical sciences. Oxford: Blackwell Science; 2000.Google Scholar
  11. 11.
    Smith-Thomas L, Richardson P, Thody AJ. Human ocular melanocytes and retinal pigment epithelial cells differ in their melanogenic properties in vivo and in vitro. Curr Eye Res. 1996;15(11):1079–91.CrossRefGoogle Scholar
  12. 12.
    Bulbul B, Baykara M, Ercan I, et al. Vitiligo and ocular findings: a study on possible. Assoc J Eur Acad Dermatol Venereol. 2006;20:829–33.Google Scholar
  13. 13.
    Boissy RE, Hornyak TJ. Extracutaneous melanocytes. In: Nordlund JJ, Boissy RE, Hearing VJ, editors. The pigmentary system: physiology and pathophysiology. Oxford: Blackwell Scientific; 2006.Google Scholar
  14. 14.
    Wakamatsu K, Hu DN, McCormick SA, et al. Characterization of melanin in human iridal and choroidal melanocytes from eyes with various colored irides. Pigment Cell Res. 2008;21:97–105.CrossRefGoogle Scholar
  15. 15.
    Roberts JE. Ocular phototoxicity. J Photochem Photobiol B. 2001;64(2–3):136–43.CrossRefGoogle Scholar
  16. 16.
    Sliney DH. How light reaches the eye and its components. Int J Toxicol. 2002;21(6):501–9.CrossRefGoogle Scholar
  17. 17.
    Glickman RD. Phototoxicity to the retina: mechanisms of damage. Int J Toxicol. 2002;21(6):473–90.CrossRefGoogle Scholar
  18. 18.
    Nordlund JJ, Boissy RE, Hearing VJ. The pigmentary system—physiology and pathophysiology. Oxford: Oxford University Press; 1998. p. 1106.Google Scholar
  19. 19.
    Boissy RE. The melanocyte. Its structure, function, and subpopulations in skin, eyes, and hair. Dermatol Clin. 1988;6(2):161–73.CrossRefGoogle Scholar
  20. 20.
    Stjernschantz J, Alm A. Latanoprost as a new horizon in the medical management of glaucoma. Curr Opin Opthalmol. 1996;7(2):11–7.CrossRefGoogle Scholar
  21. 21.
    Stjernschantz JW, Albert DM, Hu DN, et al. Mechanism and clinical significance of prostaglandin-induced iris pigmentation. Surv Ophthalmol. 2002;47(Suppl. 1):S162–75.CrossRefGoogle Scholar
  22. 22.
    Drago F, Marino A, La Manna C. Alpha-methyl-p-tyrosine inhibits latanoprost induced melanogenesis in vitro. Exp Eye Res. 1999;68(1):85–90.CrossRefGoogle Scholar
  23. 23.
    Nakazawa M, Tsuchiya M, Hayasaka S, et al. Tyrosinase activity in the uveal tissue of the adult bovine eye. Exp Eye Res. 1985;41(2):249–58.CrossRefGoogle Scholar
  24. 24.
    Lindquist NG, Larsson BS, Stjernschantz J, et al. Age-related melanogenesis in the eye of mice, studied by microautoradiography of 3H-methimazole, a specific marker of melanin synthesis. Exp Eye Res. 1998;67(3):259–64.CrossRefGoogle Scholar
  25. 25.
    Boissy RE. Non-skin melanocytes in vitiligo. In: Vitiligo. Berlin: Springer; 2010. p. 73–7.CrossRefGoogle Scholar
  26. 26.
    Schubert HD. Structure and function of the neural retina. In: Yanoff M, Duker JS, editors. Ophthalmology. 3rd ed. Edinburgh: Mosby Elsevier, Elsevier Inc.; 2009. p. 511–21.Google Scholar
  27. 27.
    Cowan CL, Halder RM, Grimes PE, et al. Ocular disturbances in vitiligo. J Am Acad Dermatol. 1986;15:17–24.. 16 in book.CrossRefGoogle Scholar
  28. 28.
    Albert DM, Nordlund JJ, Lerner AB. Ocular abnormalities occurring with vitiligo. Ophthalmology. 1979;86:1145–58.CrossRefGoogle Scholar
  29. 29.
    Albert DM, Wagoner MD, Pruett RC, et al. Vitiligo and disorders of the retinal pigment epithelium. Br J Ophthalmol. 1983;67:153–6.CrossRefGoogle Scholar
  30. 30.
    Biswas G, Barbhuiya JN, Biswas MC, et al. Clinical pattern of ocular manifestations in vitiligo. J Indian Med Assoc. 2003;101:478–80.PubMedGoogle Scholar
  31. 31.
    Bulbul Baskan E, Baykara M, Ercan I, et al. Vitiligo and ocular findings: a study on possible associations. J Eur Acad Dermatol Venereol. 2006;20:829–33.PubMedGoogle Scholar
  32. 32.
    Ayotunde A, Olakunle G. Ophthalmic assessment in black patients with vitiligo. J Natl Med Assoc. 2005;97:286–7.PubMedPubMedCentralGoogle Scholar
  33. 33.
    Karadag R, Esmer O, Karadag AS, et al. Evaluation of ocular findings in patients with vitiligo. Int J Dermatol. 2016;55:351–5.CrossRefGoogle Scholar
  34. 34.
    Dogan AS, Atacan D, Durmazlar SPK, et al. (2015) Evaluation of dry eye findings in patients with vitiligo. Pak J Med Sci. 2015;31(3):587–91.PubMedPubMedCentralGoogle Scholar
  35. 35.
    Duplancić D, Rogosić V, Puizina-Ivić N, et al. Prognostic value of ophthalmic artery color Doppler sonography for progression to glaucoma in vitiligo patients. Acta Med Croatica. 2013;67(1):47–52.PubMedGoogle Scholar
  36. 36.
    Perossini M, Turio E, Perossini T, et al. Vitiligo: ocular and electrophysiological findings. G Ital Dermatol Venereol. 2010;145(2):141–9.PubMedGoogle Scholar
  37. 37.
    Park S, Albert DM, Bolognia JL. Ocular manifestations of pigmentary disorders. Dermatol Clin. 1992;10(3):609–22.CrossRefGoogle Scholar
  38. 38.
    Hilding DA, Ginzberg RD. Pigmentation of the striavascularis. The contribution of neural crest melanocytes. Acta Otolaryngol (Stockh). 1977;84:24–37.CrossRefGoogle Scholar
  39. 39.
    Mackenzie MA, Jordan SA, Budd PS, et al. Activation of the receptor tyrosine kinase kit is required for the proliferation of melanoblasts in the mouse embryo. Dev Biol. 1997;192:99–107.CrossRefGoogle Scholar
  40. 40.
    Bondurand N, Pingault V, Goerich DE, et al. Interaction among SOX10, PAX3 and MITF, three genes altered in Waardenburg syndrome. Hum Mol Genet. 2000;9:1907–17.CrossRefGoogle Scholar
  41. 41.
    Potterf SB, Gurumura M, Dunn KJ, et al. Transcription factor hierarchy in Waardenburg syndrome: regulation of MITF expression by SOX10 and PAX3. Hum Genet. 2000;107:1–6.CrossRefGoogle Scholar
  42. 42.
    Cable J, Steel KP. Identification of two types of melanocyte within the striavascularis of the mouse inner ear. Pigment Cell Res. 1991;4:87–101.CrossRefGoogle Scholar
  43. 43.
    Sage CL, Marcus DC. Immunolocalization of CIC-K chloride channel in strial marginal cells and vestibular dark cells. Hear Res. 2001;160(1–2):1–9.CrossRefGoogle Scholar
  44. 44.
    Marcus DC, Wu T, Wangemann P, et al. KCNJ10 (Kir4.1) potassium channel knockout abolishes endocochlearpotential. Am J Physiol Cell Physiol. 2002;282(2):C403–7.CrossRefGoogle Scholar
  45. 45.
    Momiyama J, Hashimoto T, Matsubara A, et al. Leupeptin, a calpain inhibitor, protect inner ear hair cells from aminoglycoside ototoxicity. Tohoku J Exp Med. 2006;209:89–97.CrossRefGoogle Scholar
  46. 46.
    Furuta H, Luo L, Hepler K, Ryan AF. Evidence for differential regulation of calcium by outer versus inner hair cells: plasma membrane Ca-ATPase gene expression. Hear Res. 1998;123:w10–26.CrossRefGoogle Scholar
  47. 47.
    Seagle B-LL, et al. Melanin photoprotection in the human retinal pigment epithelium and its correlation with light-induced cell apoptosis. Proc Natl Acad Sci U S A. 2005;102:25–30.CrossRefGoogle Scholar
  48. 48.
    Nosanchuk JD, Casadevall A. Impact of melanin on microbial virulence and clinical resistance to antimicrobial compounds. Antimicrob Agents Chemother. 2006;11:3519–28.CrossRefGoogle Scholar
  49. 49.
    Nosanchuk JD, Casadevall A. The contribution of melanin to microbial pathogenesis. Cell Microbiol. 2003;5:203–23.CrossRefGoogle Scholar
  50. 50.
    Takeda K, Takahashi NH, Shibahara S. Neuroendocrine functions of melanocytes: beyond the skin-deep melanin maker. Tohoku J Exp Med. 2007;211:201–21.CrossRefGoogle Scholar
  51. 51.
    Aydogan K, Turan OF, Onart S, et al. Audiological abnormalities in patients with vitiligo. Clin Exp Dermatol. 2006;31:110–3.CrossRefGoogle Scholar
  52. 52.
    Escalente-Ugalde C, Poblano A, Montes de Oca E, et al. No evidence of hearing loss in patients with vitiligo. Arch Dermatol. 1991;127:1240.CrossRefGoogle Scholar
  53. 53.
    Tosti A, Bardazzi F, Tosti G, et al. Audiologic abnormalities in cases of vitiligo. J Am Acad Dermatol. 1987;17:230–3.CrossRefGoogle Scholar
  54. 54.
    Angrisani RM, Azevedo MF, Pereira LD, et al. A study on optoacoustic emissions and suppression effects in patients with vitiligo. Rev Bras Otorhinolaringol. 2009;75:111–5.CrossRefGoogle Scholar
  55. 55.
    Bassiouny A, Faris S, El-Khousht M. Hearing abnormalities in vitiligo. Egypt J Otolaryngol. 1998;15:51–60.Google Scholar
  56. 56.
    Shalaby M, El-Zarea G, Nasar A. Auditory function in vitiligo patients. Egypt Dermatol Online J. 2006;2:7.Google Scholar
  57. 57.
    Dereymaeker AM, Fryns JP, Ars J, et al. Retinitis pigmentosa, hearing loss and vitiligo: report of two patients. Clin Genet. 1989;35:387–9.CrossRefGoogle Scholar
  58. 58.
    Nikiforidis GC, Tsambaos DG, Karamitsos DS, et al. Abnormalities of the auditory brainstem response in vitiligo. Scand Audiol. 1993;22:97–100.CrossRefGoogle Scholar
  59. 59.
    Orecchia G, Marelli MA, Fresa D, et al. Audiologic disturbances in vitiligo (letter to the editor). J Am Acad Dermatol. 1989;21:1317–8.CrossRefGoogle Scholar
  60. 60.
    Ardic FN, Aktan S, Kara CO, et al. High-frequency hearing and reflex latency in patients with pigment disorder. Am J Otolaryngol. 1998;19:365–9.CrossRefGoogle Scholar
  61. 61.
    Anbar TS, El-Badry MM, McGrath JA, et al. Most individuals with either segmental or non-segmental vitiligo display evidence of bilateral cochlear dysfunction. Br J Dermatol. 2015;172(2):406–11.CrossRefGoogle Scholar
  62. 62.
    Takeda K, Yokoyama S, Aburatani H, et al. Lipocalin-type prostaglandin D synthase as a melanocyte marker regulated by MITF. Biochem Biophys Res Commun. 2006;339:1098–106.CrossRefGoogle Scholar
  63. 63.
    Urade Y, Hayaishi O. Biochemical, structural, genetic, physiological, and pathophysiological features of lipocalin-type prostaglandin D synthase. Biochim Biophys Acta. 2000;1482:259–71.CrossRefGoogle Scholar
  64. 64.
    Wakamatsu K, Fujikawa K, Zucca L, et al. The structure of neuromelanin as studied by chemical degrative methods. J Neurochem. 2003;86:1015–23.CrossRefGoogle Scholar
  65. 65.
    Hirano A. Neurons and astrocytes. In: Davis RL, Robertson DM, editors. Textbook of neuropathology. 2nd ed. Baltimore, MD: Williams & Wilkins; 1991. p. 15–8.Google Scholar
  66. 66.
    Burger PC, Scheithauer BW, Vogel FS. Surgical pathology of the nervous system and its coverings, vol. 3. New York, NY: Churchill Livingstone; 1999. p. 115–7.Google Scholar
  67. 67.
    Zecca L, Fariello R, Riederer P, et al. The absolute concentration of nigralneuromelanin, assayed by a new sensitive method, increases throughout the life and is dramatically decreased in Parkinson’s disease. FEBS Lett. 2002;510:216–20.CrossRefGoogle Scholar
  68. 68.
    Zucca FA, Giaveri G, Gallorini M, et al. The neuromelanin of human substantia nigra: physiological and pathogenic aspects. Pigment Cell Res. 2004;17:610–7.CrossRefGoogle Scholar
  69. 69.
    Rozanowska M, Sarna T, Land EJ, et al. Free radical scavenging properties of melanin interaction of eu- and pheo-melanin models with reducing and oxidizing radicals. Free Radic Biol Med. 1999;26(5–6):518–25.CrossRefGoogle Scholar
  70. 70.
    Enochs WS, Petherick P, Bogdanova A, et al. Paramagnetic metal scavenging by melanin: MR imaging. Radiology. 1997;204(2):417–23.CrossRefGoogle Scholar
  71. 71.
    Lucena DR, Paula JS, Silva GCM, et al. Síndrome de Vogt-Koyanagi-Harada incompletaassociada a HLA DRB1*01 emcriança de quatroanos de idade: relato de caso. Arq Bras Oftalmol. 2007;70:340–2.CrossRefGoogle Scholar
  72. 72.
    Park HY, Perez JM, Laursen R, Hara M, et al. Protein kinase C-beta activates tyrosinase by phosphorylating serine residues in its cytoplasmic domain. J Biol Chem. 2009;274:16470–8.CrossRefGoogle Scholar
  73. 73.
    Prignano F, Betts CM, Lotti T. Vogt-Koyanagi-Harada disease and vitiligo: where does the illness begin? J Electron Microsc (Tokyo). 2008;57(1):25–31.CrossRefGoogle Scholar
  74. 74.
    Waardenburg PJ. A new syndrome combining developmental anomalies of the eyelids, eyebrows and nose root with pigmentary defects of the iris and head hair and with congenital deafness. Am J Hum Genet. 1951;3:195–253.PubMedPubMedCentralGoogle Scholar
  75. 75.
    Andrade A, Pithon M. Alezzandrini syndrome: report of a sixth clinical case. Dermatology. 2011;222:8–9.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Tag S. Anbar
    • 1
  • Rehab A. Hegazy
    • 2
  • Suzan Shalaby
    • 2
  1. 1.Department of Dermatology and Andrology, Faculty of MedicineAl Minya UniversityAl MinyaEgypt
  2. 2.Department of Dermatology, Faculty of MedicineCairo UniversityCairoEgypt

Personalised recommendations