Lipofuscin in Aged and AMD Eyes

  • C. Kathleen Dorey
  • Giovanni Staurenghi
  • Francois C. Delori

Abstract

AMD is a progressive degeneration of the retina which preferentially and initially affects the macula but ultimately involves the fovea (1). The leading cause of visual impairment for individuals over 65, it will affect an estimated 8 million Americans in the next 20 years (2). The majority of these will experience a gradual erosion of vision due to progressive atrophy of photoreceptors—causing decreased visual acuity, loss of color vision and tunnel vision; some will be legally blind (3). About 90% of legal blindness in AMD is due to exudative AMD, characterized by serous detachment of the retina, retinal pigment epithelial detachment and tears, aggressive growth of new blood vessels from the choroid into the subretinal space, and disciform scaring. Fortunately, only 5–10% of patients will develop exudative AMD (4,5) While laser photocoagulation can delay and/or reduce the consequent visual loss, the prognosis remains grim—most will be blind (6). Presently, there is no medical treatment to stop or slow the course of this disease nor any known prevention.

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References

  1. 1.
    S.H Sarks and J.P. Sarks, Age-related macular degeneration: atrophic form, in “Volume Two Medical Retina,” A.P. Schachat, R.P. Murphy, A. Patz, eds, in “Retina,” S.J. Ryan, ed., C.V. Mosby Co., St. Louis,(1989).Google Scholar
  2. 2.
    Pizarello, L.D. The dimensions of the problem of eye disease among the elderly., Ophthalmol., 94:1191 (1987).Google Scholar
  3. 3.
    Macular Photocoagulation Study Group. Argon laser photocoagulation for neovascular maculopathy, Arch. Ophthalmo 1109:1109 (1991).Google Scholar
  4. 4.
    L.G. Hyman, A.M. Lilienfeld, F.L. Ferris, III and S.L. Fine, Senile macular degeneration, a case-control study, Am. J. Epidemiol. 118:213 (1983).PubMedGoogle Scholar
  5. 5.
    R. Klein, B.K. Klein, and K.L.P. Linton, Prevalence of age-related maculopathy. The Beaver Dam eye study, Ophthalmol. 99:933 (1992).Google Scholar
  6. 6.
    Macular Photocoagulation Study Group, Subfoveal recurrent neovascular lesions in age-related macular degeneration. Guidelines for evaluation and treatment in the Macular Photocoagulation Study, Arch. Ophthalmol. 109:1242 (1991).CrossRefGoogle Scholar
  7. 7.
    S.H. Sarks, Drusen and their relationship to senile macular degeneration, Aust J Ophthalmol. 8:117 (1980).PubMedCrossRefGoogle Scholar
  8. 8.
    W.R. Green, P.H. McDonnell, and Y.H. Yeo, Pathologic features of senile macular degeneration. Ophthalmol. 92:615 (1985).Google Scholar
  9. 9.
    D. Pauleikoff, M.J. Barondes, D. Minassian, I.H. Chisholm, A.C. Bird, Drusen as risk factors in age-related macular disease. Am. J. Ophthalmol. 109:38 (1990).Google Scholar
  10. 10.
    M.J. Hogan, Role of the retinal pigment epithelium in macular disease, Trans. Am. Acad. Ophthalmol. Otolaryngol. 76:64 (1972).PubMedGoogle Scholar
  11. 11.
    R.W. Young, Pathophysiology of age-related macular degeneration, Surv. Ophthalmol. 31:291 (1987).PubMedCrossRefGoogle Scholar
  12. 12.
    L. Feeney-Burns and M.R. Ellersieck MR, Age-related changes in the ultrastructure of Bruch’s membrane, Am. J. Ophthalmol. 100: 686 (1985).PubMedGoogle Scholar
  13. 13.
    J.J. Weiter, F.C. Delori, G.L. Wing and K.A. Fitch, Retinal pigment epithelial lipofuscin and melanin and choroidal melanin in human eyes. Invest. Ophthalmol. Vis. Sci. 27:145 (1986).PubMedGoogle Scholar
  14. 14.
    L. Feeney-Burns, E.S. Hilderbrand, and S. Eldridge, Aging human RPE: morphometric analysis of macular, equatorial and peripheral cells. Invest Ophthalmol Vis. Sci. 25:195, (1984).PubMedGoogle Scholar
  15. 15.
    C.K. Dorey, G. Wu, D. Ebenstein, A. Garsd, and J.J. Weiter, Cell loss in the aging retina. Relationship to lipofuscin accumulation and macular degeneration. Invest. Ophthalmol. Vis. Sci. 30:1691 (1989).PubMedGoogle Scholar
  16. 16.
    J.J. Weiter, F. Delori, and C.K. Dorey, Central sparing in annular macular degeneration, Am. J. Ophthalmol. 106:286 (1988).PubMedCrossRefGoogle Scholar
  17. 17.
    B.E. Klein and R Klein: Cataracts and macular degeneration in older Americans. Arch. Ophthalmol. 100:571 (1982).PubMedCrossRefGoogle Scholar
  18. 18.
    F.L. Ferris, III. Senile macular degeneration: review of epidemiologic features, Am. J. Epidemiol. 118:132 (1983).PubMedGoogle Scholar
  19. 19.
    Z. Gregor and L. Joffe, Senile macular changes in the black African, Br. J. Ophthalmol. 62:547 (1978).PubMedCrossRefGoogle Scholar
  20. 20.
    J.J. Weiter, F.C. Delori, G.L. Wing, K.A. Fitch, Relationship of senile macular degeneration to ocular pigmentation, Am. J. Ophthalmol. 99:185 (1985).PubMedGoogle Scholar
  21. 21.
    A.P. Schachat, M.C. Leske, A. Connell, V. Squicciarini, N. Oden, and the Barbados Eye Study Group, Prevalence of macular degeneration in a black population, Invest. Ophthalmol. Vis. Sci. Abstracts 33:801 (1992).Google Scholar
  22. 22.
    G.L. Wing, G.C. Blanchard, and J.J. Weiter, The tcpography and age relationship of lipofuscin concentration in the retinal pigment epithelium, Invest. Ophthalmol. Vis. Sci. 17:601 (1978).PubMedGoogle Scholar
  23. 23.
    N.M. Bressler, S.B. Bressler, and S.F. Fine, Age-related macular degeneration, Surv. Ophthalmol. 32:375 (1988).PubMedCrossRefGoogle Scholar
  24. 24.
    M.J. Elman and S.L. Fine, Exudative age-related macular degeneration, in “Volume Two Medical Retina,” A.P. Schachat, R.P. Murphy, A. Patz, eds, in “Retina,” S.J. Ryan, ed., C.V. Mosby Co., St. Louis, (1989).Google Scholar
  25. 25.
    S.H. Sarks, Evolution of geographic atrophy, Eye 2:552 (1988).PubMedCrossRefGoogle Scholar
  26. 26.
    G.E. Eldred and M.L. Katz, Lipofuscinogenesis in the RPE, in “Lipofuscin - 1987. State of the Art.” Zs-I. Nagy, ed. Excerpta Medica, New York, pp 185 (1988).Google Scholar
  27. 27.
    L. Feeney-Burns and G.E. Eldred. The fate of the phagosome: conversion to “age pigment” and impact in human retinal pigment epithelium, Trans. Ophthalmol. Soc. UK 103:416 (1984).Google Scholar
  28. 28.
    M.L. Katz and G.E. Eldred, Retinal light damage reduces autofluorescent pigment deposition in the retinal pigment epithelium, Invest. Ophthal. Vis. Sci. 30:37 (1989).PubMedGoogle Scholar
  29. 29.
    M.L. Katz, C.M. Drea, G.E. Eldred, H.H. Hess, W.G. Robison, Jr, Influence of early photoreceptor degeneration on lipofuscin accumulation in the retinal pigment epithelium. Exp. Eye Res. 43:561 (1986).PubMedCrossRefGoogle Scholar
  30. 30.
    W.G. Robison, Jr, T. Kuwubara, and J.B. Bieri, Deficiencies of Vitamins E and A in the rat: Retinal damage and lipofuscin accumulation. Invest. Ophthal. Vis. Sci. 19: 1030(1980).Google Scholar
  31. 31.
    M.L. Katz, KR. Parker, G.J. Handelman, T.L. Bramel, and E.A. Dratz, Effects of antioxidant deficiency on the retina and retinal pigment epithelium of albino rats: A light and electron microscopic study, Exp Eye Res. 34:339 (1982)PubMedCrossRefGoogle Scholar
  32. 32.
    L. Feeney, Lipofuscin and melanin of human retinal pigment epithelium, Invest. Ophthalmol. Vis. Sci.,17:583 (1978)PubMedGoogle Scholar
  33. 33.
    C.K. Dorey and S.A. Curran. Unpublished results.Google Scholar
  34. 34.
    C.K. Dorey and D.B. Ebenstein, Quantitative multispectral analysis of discrete subcellular particles by digital imaging fluorescence microscopy, in ‘Visual Communications and Image Processing,“ R. Tsing, ed.,Soc. Photoo-optical and Instrumentation Engineers, Bellingham, WA (1988).Google Scholar
  35. 35.
    E. Holtzman, “Lysosomes,” Plenum Press, New York, (1989).Google Scholar
  36. 36.
    R.E.W. Watts and D.A. Gibbs, “Lysosomal Storage Diseases: Biochemical and Clinical Aspects,” Taylor and Francis, London, pp 1–8, 201, (1986).Google Scholar
  37. 37.
    D. Armstrong, N. Koppang, and J. Rider, “Ceroid lipofuscinosis (Batten’s disease)” Elsevier, Amsterdam, (1982).Google Scholar
  38. 38.
    R.O. Brady, Lysosomal storage diseases. Pharmacol. Therapeutics 19:327 (1982) (REVIEW).CrossRefGoogle Scholar
  39. 39.
    S. O’Gorman, W.A. Flaherty, G.A. Fishman, and E.L. Berson, Histopathologic findings in Best’s vitelliform macular dystrophy, Arch. Ophthalmol. 106:1261 (1988).PubMedCrossRefGoogle Scholar
  40. 40.
    T.A. Weingeist, J.L. Kobrin, and K.E. Watz, Histopathology of Best’s macular dystrophy, Arch. Ophthalmol. 100:108 (1982).Google Scholar
  41. 41.
    R.C. Eagle, Jr., A.C. Lucier, V.B. Bernadino, Jr. and M. Yanoff, Retinal pigment epithelial abnormalities in fundus flavimaculatus. Ophthalmol. 87:1189 (1980).Google Scholar
  42. 42.
    S.E. Nilsson and S. Jagell, Lipofuscin and melanin content of the retinal pigment epithelium in a case of Sjorgen-Larsson syndrome, Br. J. Ophthalmol. 71:224, (1987).PubMedCrossRefGoogle Scholar
  43. 43.
    M.F. Rabb, M.O.M. Tso, and G.A. Fishman, Cone-rod dystrophy. A clinical and histopathologic report, Ophthalmol. 93:1443(1986).Google Scholar
  44. 44.
    D. Samuelson, W.W. Dawson, A.I. Webb, J. Dowson, R Jolley, and D. Armstrong. Retinal pigment epithelial dysfunction in early ovine ceroid lipofuscinosis: electrophysiologic correlates, Ophthalmologia 190:150 (1985).CrossRefGoogle Scholar
  45. 45.
    H.R. Taylor, S. West, B. Munoz, F.S. Rosenthal, S.B. Bressler, N.M. Bressler, The long term effects of visible light on the eye. Arch. Ophthalmol. 110:99 (1992).PubMedCrossRefGoogle Scholar
  46. 46.
    W.T. Ham, J.J. Ruffolo, Jr., H.A. Mueller, and D. Guerry, The nature of retinal radiation damage: dependence on wavelength, power level and exposure time. Vis. Res. 20:1163 (1980).CrossRefGoogle Scholar
  47. 47.
    L. Hyman, O. He, R. Grimson, N. Oden, A.P. Schachat, M.C. Leske, and the Age-related Macular Degeneration Risk Factors Study Group, Risk factors for age-related maculopathy, Invest. Ophthalmol. Vis. Sci (SUPPL) 33:801 (1992).Google Scholar
  48. 48.
    R. Russell-Briefel, M.W. Bates, and L.H. Kuller, The relationship of plasma carotenoids to health and biochemical factors in middle-aged men. Am. J. Epidemiol. 122:741 (1985).PubMedGoogle Scholar
  49. 49.
    J. Goldberg, G. Flowerdew, E. Smith, J.A. Brody, and M.O. Tso, Factors associated with age-related macular degeneration. An analysis of data from the first National Health and Nutrition Examination Survey, Am. J. Epidemiol. 128:700, 1988.PubMedGoogle Scholar
  50. 50.
    C.K. Dorey, A. Elsner, G. Staurenghi, and F.C. Deliori, What patterns the accumulation of RPE lipofuscin? Exp. Eye Res (SUPPL). 55:710 (1992).Google Scholar
  51. 51.
    C.K. Dorey, G. Staurenghi, F.C. Delori, J.R. Sarks, S.H. Sarks, Lipofuscin distribution in aging and AMD eyes. Invest. Ophthalmol. Vis. Sci. (SUPPL) 33:#2677 (1992).Google Scholar
  52. 52.
    F.C. Delori, K.A. Fitch, and J.M. Gorrand, In-Vivo characterization of intrinsic fundus fluorescence, Noninvasive Assessment of the Visual System, Opt. Soc. Amer. Tech. Dig. 3:72 (1990).Google Scholar
  53. 53.
    F.C. Delori, Fluorophotometer for noninvasive measurement of RPE lipofuscin. Noninvasive Assessment of the Visual System, Opt. Soc. Amer. Tech. Dig. 1:164 (1992).Google Scholar
  54. 54.
    G.E. Eldred and M.L. Katz, Fluorophores of the human retinal pigment epithelium: Separation and spectral characterization, Exp. Eye Res., 47:71 (1988).PubMedCrossRefGoogle Scholar
  55. 55.
    G.E. Eldred, Vitamins A and E in PRE lipofuscin formation and implications for age-related macular degeneration. Progr. Clin. Biol. Res. 314;113 (1989).Google Scholar
  56. 56.
    M.L. Katz and M. Norberg, Influence of dietary vitamin A on autofluorescence of leupeptin-induced inclusions in the retinal pigment epithelium Exp. Eye Res. 54:239 (1992).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • C. Kathleen Dorey
    • 2
    • 3
  • Giovanni Staurenghi
    • 2
    • 3
    • 4
  • Francois C. Delori
    • 1
    • 3
  1. 1.Schepens Eye Research InstituteBiomedical Physics and Macular Degeneration Research CenterBostonUSA
  2. 2.Schepens Eye Research InstituteBiochemistry and Cell Biology Macular Degeneration Research CenterBostonUSA
  3. 3.Department of OphthalmologyHarvard Medical SchoolBostonUSA
  4. 4.Istituto di Scienze BiomedicheClinica Oculistica Universitâ degli Studi di MilanoMilanoItaly

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