Advertisement

Drusenoid maculopathy in rhesus monkeys: autofluorescence, lipofuscin and drusen pathogenesis

  • Peter GourasEmail author
  • Lena Ivert
  • Julie A. Mattison
  • Donald K. Ingram
  • Martha Neuringer
Retinal Disorders

Abstract

Purpose

To examine patterns of retinal pigment epithelial autofluorescence and lipofuscin accumulation in relation to drusen and to explore the pathogenesis of drusen in rhesus monkeys.

Methods

The macular areas of six rhesus monkeys, euthanized at 19 to 28 years of age, were studied by bright field and fluorescence light microscopy and transmission electron microscopy.

Results

There was strong autofluorescence in the retinal epithelium that tended to diminish over drusen. Electron microscopy revealed that all retinal epithelial cells had large concentrations of lipofuscin bodies. The epithelial cells overlying drusen, however, tended to have less lipofuscin than epithelial cells not associated with drusen. Electron microscopy revealed that the epithelial cells overlying drusen were losing segments of cytoplasm containing lipofuscin bodies. Macrophage-like cells were consistently present in Bruch’s membrane microns away from this lipofuscin-containing cytoplasmic material.

Conclusions

Retinal epithelial cells overlying drusen have less lipofuscin than neighboring epithelial cells. The loss of lipofuscin seems due to a loss of cytoplasm containing lipofuscin that contributes to drusen formation. Macrophages in Bruch’s membrane may be responsible for removing this lipofuscin debris. The results support in vivo studies showing reduced autofluorescence over drusen and support the “budding” of epithelial cytoplasm as a source of drusen material.

Keywords

Macula Age-related macular degeneration Drusen Lipofuscin Autofluorescence Monkey 

Notes

Acknowledgements

We thank Kristy Braun and Hild Kjeldbye for technical assistance and NEI grants EY015293 and RR00163, The Foundation Fighting Blindness and Research to Prevent Blindness Inc. for support.

References

  1. 1.
    Bok D (2002) New insights and new approaches toward the study of age-related macular degeneration. Proc Natl Acad Sci USA 99:14619–14621. doi: 10.1073/pnas.242607899 PubMedCrossRefGoogle Scholar
  2. 2.
    Burns R, Feeney-Burns L (1980) Clinico-morphologic correlations of drusen of Bruch’s membrane. Trans Am Ophthalmol Soc 78:206–222PubMedGoogle Scholar
  3. 3.
    Delori FC, Fleckner MR, Goger DG, Weiter JJ, Dorey CK (2000) Autofluorescence distribution associated with drusen in age-related macular degeneration. Invest Ophthalmol Vis Sci 41:496–504PubMedGoogle Scholar
  4. 4.
    Donders FC (1855) Beitrage zur pathologischen Anatomie des Auges. Graefes Arch Clin Exp Ophthalmol 2:106–118. doi: 10.1007/BF02720791 Google Scholar
  5. 5.
    Farkas TG, Sylvester V, Archer D (1971) The ultrastructure of drusen. Am J Ophthalmol 71:1196–1205PubMedGoogle Scholar
  6. 6.
    Gouras P, Ivert L, Mattison JA, Landauer N, Neuringer M (submitted) Drusenoid maculopathy in rhesus monkeys: effects of age, gender and dietGoogle Scholar
  7. 7.
    Hageman GS, Luthert PJ, Chong VNH, Johnson LV, Anderson DH, Mullins RF (2001) An integrated hypothesis that considers drusen as biomarkers of immune-mediated processes at the RPE-Bruch’s membrane interface at in aging and age-related macular degeneration. Prog Retin Eye Res 20:705–732. doi: 10.1016/S1350-9462(01)00010-6 PubMedCrossRefGoogle Scholar
  8. 8.
    Hogan MJ (1967) Bruch’s membrane and disease of the macula: Role of elastic tissue and collagen. Trans Ophthalmol Soc U K 87:113–161PubMedGoogle Scholar
  9. 9.
    Ishibashi T, Sorgente N, Patterson R, Ryan S (1986) Pathogenesis of drusen in the primate. Invest Ophthalmol Vis Sci 27:184–193PubMedGoogle Scholar
  10. 10.
    Killingsworth MC, Sarks JP, Sarks SH (1990) Macropages related to Bruch’s membrane in age-related macular degeneration. Eye 4:613–621PubMedGoogle Scholar
  11. 11.
    Mattison JA, Lane MA, Roth GS, Ingram DK (2003) Calorie restriction in rhesus monkeys. Exp Gerontol 38:35–46. doi: 10.1016/S0531-5565(02)00146-8 PubMedCrossRefGoogle Scholar
  12. 12.
    Muller H (1856) Anatomische Beiträge zur Ophthalmologie. Graefes Arch Clin Exp Ophthalmol 2:1–69. doi: 10.1007/BF02720657 Google Scholar
  13. 13.
    Spencer WH (1965) Pathogenesis of macular degeneration: light microscopy. Trans Am Acad Ophthalmol Otolaryngol 69:662–667PubMedGoogle Scholar
  14. 14.
    Suter M, Remé CE, Grimm C, Wenzel A, Jaattela M, Esser P, Kociak N, Leist M, Richter C (2000) Age-related macular degeneration: The lipofuscin component A2E detaches pro-apoptotic proteins from mitochondria and induces apoptosis in mammalian retinal pigment epithelial cells. J Biol Chem 277:39625–39630CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Peter Gouras
    • 1
    Email author
  • Lena Ivert
    • 2
  • Julie A. Mattison
    • 3
  • Donald K. Ingram
    • 4
  • Martha Neuringer
    • 5
    • 6
  1. 1.Department of OphthalmologyColumbia UniversityNew YorkUSA
  2. 2.Department of OphthalmologySt Erik’s Eye Hospital, Karolinska InstituteStockholmSweden
  3. 3.Laboratory of Experimental Gerontology, National Institute on AgingBaltimoreUSA
  4. 4.Nutritional Neuroscience and Aging Laboratory, Pennington Biomedical Research CenterLouisiana State University SystemBaton RougeUSA
  5. 5.Division of Neuroscience, Oregon National Primate Research CenterOregon Health & Science UniversityBeavertonUSA
  6. 6.Department of OphthalmologyOregon Health & Science UniversityBeavertonUSA

Personalised recommendations