Morphological and Biochemical Studies of the Retinal Degeneration in the Vitiligo Mouse

A Model with Perturbed Retinoid Metabolism
  • Sylvia B. Smith
  • Barbara N. Wiggert

Abstract

The vitiligo mouse has been studied since the mid 1980’s for the depigmentary condition of its skin and fur. As such, it is a promising model for the human skin disease vitiligo ( 1 ). Vitiligo may occur in isolation or in combination with other disorders, including retinal degeneration (Vogt-Koyanagi-Harada syndrome) (2). In 1988, Dr. Richard Sidman and co-workers provided a preliminary report in Mouse News Letter that the vitiligo mouse had a slow progressive retinal degeneration (3). We obtained breeding pairs from Dr. Sidman and set out to characterize the retinal degeneration in this mouse and to determine the etiology of the disease with the hope of eventually designing strategies to treat the disorder. This chapter will review our findings about the morphologic, electrophysiologic and biochemical characteristics of this mutant with particular emphasis on promising results from studies of retinoid metabolism.

Keywords

Fluoride Retina Leucine Photolysis Lecithin 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Lemer AB, Shiohara T, Boissy RE, Jacabson KA, Lamoreux ML, Moellmann GE. (1986) A mouse model for vitiligo. J. Invest. Dermatol. 87, 299–304.CrossRefGoogle Scholar
  2. 2.
    Nussenblatt RB, Palestine AG. (1989) Vogt-Koyanagi-Hirada syndrome. In Retina. SJ Ryan (Ed.) Mosby, St Louis, pp. 723–728.Google Scholar
  3. 3.
    Sidman RL, Neumann P. (1988) Vitiligo: a new retinal degeneration mutation. Mouse News Letter 81, 60.Google Scholar
  4. 4.
    Smith SB. (1992) C57BL/6J-vit/vit mouse model of retinal degeneration: Light microscopic analysis and evaluation of rhodopsin levels. Exp. Eye Res. 55, 903–910.PubMedCrossRefGoogle Scholar
  5. 5.
    Smith SB. (1995) Evidence of a difference in photoreceptor cell loss in the peripheral versus posterior regions of the vitiligo (C57BL/6J-mivit/mivit) mouse retina. Exp. Eye Res. (In press).Google Scholar
  6. 6.
    Boissy RE, Moellmann GE, Lerner AB. (1987) Morphology of melanocytes in hair bulbs and eyes of vitiligo mice. Am. J. Pathol. 127, 380–388.PubMedCentralPubMedGoogle Scholar
  7. 7.
    Smirnakis SM, Tang M, Sidman RL. (1991) Abnormalities of pigment epithelium precede photoreceptor cell degeneration in vitiligo mutant mice. Invest. Ophthalmol. Vis. Sci. (Suppl).31, 298.Google Scholar
  8. 8.
    Smith SB, Hamasaki DI. (1994) Electroretinographic study of the C57BL/6-mivit/mivit mouse model of retinal degeneration. Invest. Ophthalmol. Vis Sci. 35, 3119–3123.PubMedGoogle Scholar
  9. 9.
    Smith SB, Cope BK, McCoy JR, McCool DJ, Defoe DM. (1994) Reduction of phagosomes in the vitiligo mouse model of retinal degeneration. Invest. Ophthalmol. Vis. Sci. 35, 3625–3632.PubMedGoogle Scholar
  10. 10.
    Herron WL, Riegel BW, Myers OE, Rubin ML. (1969) Retinal dystrophy in the rat — a pigment epithelial disease. Invest. Ophthalmol. Vis. Sci. 8, 595–604.Google Scholar
  11. 11.
    Smith SB, Defoe DM. (1995) Autoradiographic and biochemical assessment of rod outer segment renewal in the vitiligo (mivit/mivit) mouse model of retinal degeneration. Exp. Eye Res. (In press).Google Scholar
  12. 12.
    Smith SB, McCoy JR, Cope BK. (1993) Opsin synthesis in the C57BL/6-mivit/mivit mouse model of retinal degeneration. Curr. Eye Res., 12, 711–717.PubMedCrossRefGoogle Scholar
  13. 13.
    Smith SB, Cope BK, McCoy JR. (1994) Effects of dark-rearing on the retinal degeneration of the C57BL/6-mivit/mivit mouse. Exp. Eye Res. 58, 77–84.PubMedCrossRefGoogle Scholar
  14. 14.
    Smith SB, Duncan T, Kutty G, Kutty RK, Wiggert B. (1994) Increase in retinyl palmitate concentration in eyes and livers and the concentration of interphotoreceptor retinoid-binding protein in eyes of vitiligo mutant mice. Biochem. J. 300, 63–68.PubMedCentralPubMedGoogle Scholar
  15. 15.
    Saari JC, Bredberg DL, Farrell DF. (1993) Retinol esterification in bovine retinal pigment epithelium: Reversibility of lecithnr.retinol acyltransferase Biochem. J. 291, 697–700.PubMedCentralPubMedGoogle Scholar
  16. 16.
    Olson JA. (1969) Metabolism and function of vitamin A. Fed Proc. Fed. Am. Soc. Exp. Biol,. 28, 1670–1677.Google Scholar
  17. 17.
    Duncan T, Green JB, Green MH. (1993) Liver vitamin A levels in rats are predicted by a modified isotope dilution technique. J. Nutr. 694–703.Google Scholar
  18. 18.
    Lamoreux ML, Boissy RE, Womack JE, Nordlund JJ. (1992) The vit gene maps to the mi (microphthalmia) locus of the laboratory mouse. J. Hered. 83, 435–439.PubMedGoogle Scholar
  19. 19.
    Tang M, Neumann PE, Kosaras B, Taylor BA, Sidman RL. (1992) Vitiligo maps to mouse chromosome 6 within or close to the mi locus. Mouse Genome, 90, 441–443.Google Scholar
  20. 20.
    Hodgkinson CA, Moore KJ, Nakayama A, Steingrimsson E, Copeland NG, Jenkins NA, Arnheiter H. (1993) Mutations at the mouse microphthalmia locus are associated with defects in a gene encoding a novel basic-helix-loop-helix-zipper protein. Cell, 74, 395–404.PubMedCrossRefGoogle Scholar
  21. 21.
    Hughes MJ, Lingrel JB, Krakowsky JM, Anderson KP. (1993) A helix-loop-helix transcription factor-like gene is located at the mi locus. J. Biol. Chem. 268-20687-20690.Google Scholar
  22. 22.
    Steingrimsson E, et al (1994) Molecular basis of mouse microphthalmia (mi) mutations helps explain their developmental and phenotypic consequences. Nature Genetics 8: 256–263.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1995

Authors and Affiliations

  • Sylvia B. Smith
    • 1
    • 2
  • Barbara N. Wiggert
    • 1
    • 2
  1. 1.Department of Cellular Biology and Anatomy and OphthalmologyMedical College of GeorgiaAugustaUSA
  2. 2.Laboratory of Retinal Cell and Molecular BiologyNational Eye Institute, National Institutes of HealthBethesdaUSA

Personalised recommendations