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

  • Retinal Disorders
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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.

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References

  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

    Article  PubMed  CAS  Google Scholar 

  2. Burns R, Feeney-Burns L (1980) Clinico-morphologic correlations of drusen of Bruch’s membrane. Trans Am Ophthalmol Soc 78:206–222

    PubMed  CAS  Google Scholar 

  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 41:496–504

    PubMed  CAS  Google Scholar 

  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. Farkas TG, Sylvester V, Archer D (1971) The ultrastructure of drusen. Am J Ophthalmol 71:1196–1205

    PubMed  CAS  Google Scholar 

  6. Gouras P, Ivert L, Mattison JA, Landauer N, Neuringer M (submitted) Drusenoid maculopathy in rhesus monkeys: effects of age, gender and diet

  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

    Article  PubMed  CAS  Google Scholar 

  8. Hogan MJ (1967) Bruch’s membrane and disease of the macula: Role of elastic tissue and collagen. Trans Ophthalmol Soc U K 87:113–161

    PubMed  CAS  Google Scholar 

  9. Ishibashi T, Sorgente N, Patterson R, Ryan S (1986) Pathogenesis of drusen in the primate. Invest Ophthalmol Vis Sci 27:184–193

    PubMed  CAS  Google Scholar 

  10. Killingsworth MC, Sarks JP, Sarks SH (1990) Macropages related to Bruch’s membrane in age-related macular degeneration. Eye 4:613–621

    PubMed  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  12. Muller H (1856) Anatomische Beiträge zur Ophthalmologie. Graefes Arch Clin Exp Ophthalmol 2:1–69. doi:10.1007/BF02720657

    Google Scholar 

  13. Spencer WH (1965) Pathogenesis of macular degeneration: light microscopy. Trans Am Acad Ophthalmol Otolaryngol 69:662–667

    PubMed  CAS  Google Scholar 

  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 277:39625–39630

    Article  Google Scholar 

Download references

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.

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Authors and Affiliations

  1. Department of Ophthalmology, Columbia University, New York, NY, USA

    Peter Gouras

  2. Department of Ophthalmology, St Erik’s Eye Hospital, Karolinska Institute, Polhemsgatan 50, 112 82, Stockholm, Sweden

    Lena Ivert

  3. Laboratory of Experimental Gerontology, National Institute on Aging, 5600 Nathan Shock Drive, Baltimore, MD, 21224, USA

    Julie A. Mattison

  4. Nutritional Neuroscience and Aging Laboratory, Pennington Biomedical Research Center, Louisiana State University System, 6400 Perkins Road, Baton Rouge, LA, 70810, USA

    Donald K. Ingram

  5. Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, 505 NW 185th Avenue, Beaverton, OR, 97006, USA

    Martha Neuringer

  6. Department of Ophthalmology, Oregon Health & Science University, 505 NW 185th Avenue, Beaverton, OR, 97006, USA

    Martha Neuringer

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  1. Peter Gouras
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  2. Lena Ivert
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  3. Julie A. Mattison
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  4. Donald K. Ingram
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  5. Martha Neuringer
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Corresponding author

Correspondence to Peter Gouras.

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The authors have no proprietary interest to report.

The authors have full control of all primary data, and agree to allow Graefe’s Archive for Clinical and Experimental Ophthalmology to review our data upon request.

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Gouras, P., Ivert, L., Mattison, J.A. et al. Drusenoid maculopathy in rhesus monkeys: autofluorescence, lipofuscin and drusen pathogenesis. Graefes Arch Clin Exp Ophthalmol 246, 1403–1411 (2008). https://doi.org/10.1007/s00417-008-0911-7

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  • DOI: https://doi.org/10.1007/s00417-008-0911-7

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