Drusenoid maculopathy in rhesus monkeys (Macaca mulatta): effects of age and gender

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



To compare drusenoid maculopathy in monkeys with human age-related macular degeneration, and evaluate the influence of age, gender and caloric restriction.


Examination by indirect ophthalmoscopy, slit-lamp biomicroscopy and fundus photography, including in some cases fluorescein angiography, was performed on 61 male and 60 female rhesus macaques of ages 10–39 years. Fifty-four of the monkeys were maintained on a calorically restricted diet (approximately 30% lower than control levels) and 67 on an approximately ad libitum diet for 2–19 years, with all other environmental factors held constant. Maculopathies were graded on a 5-point scale and the effects of age, sex, and diet on prevalence and severity were examined. The retinas of six monkeys with macular drusen, 19–28 years old, were examined histologically.


Rhesus monkeys showed a high prevalence (61%) of drusenoid maculopathy. The prevalence and severity of the maculopathy increased with age (p = 0.012). Fully half of all monkeys aged 10–12 years had some detectable degree of drusen. This high prevalence in young adulthood indicates that drusen develop much earlier in rhesus monkeys than in humans, who develop early maculopathy most rapidly at 50–60 years of age, even when correcting for the 3-fold difference in lifespan. No neovascularization or geographic atrophy was found. Females had a higher prevalence and severity than males (p = 0.019). Calorically restricted monkeys had a slightly lower prevalence and severity at 10–12 years than controls, but the difference was not statistically significant. This is an on-going project, and differences between the caloric restricted and ad-lib groups may emerge as the animals age. Some monkeys developed severe maculopathy in their 20s, with others unaffected in their 30s. The histology of drusen resembled those in human retina.


Drusenoid maculopathy is common in rhesus monkeys, even in young adult life. Half of the rhesus monkeys examined have drusen at a much younger age than in humans. Severity of maculopathy was greater in female monkeys, a gender difference not consistently found in humans. No differences were detected due to caloric restriction, but a definitive test of this intervention will require a larger sample, longer period of observation, and/or an earlier institution of caloric restriction. Genetic factors are implied because with similar environments, some monkeys are affected at an early age, while older ones are not.


Macula Age-related macular degeneration Drusen Caloric restriction Diet Monkey 



Support was provided by NIH grants EY015293 and RR00163, the Intramural Research Program of the NIH, National Institute on Aging, Research to Prevent Blindness and the Foundation Fighting Blindness for support. We thank the staff and veterinarians at both sites for their highly skilled care of the monkey colonies; these studies would not have been possible without their contributions.


  1. 1.
    Anderson M, Dawson WW, Gonzales-Martinez J, Curcio CA (2006) Drusen and lipid-filled retinal pigment epithelium cells in a rhesus macula. Vet Ophthalmol 9:201–210, doi: 10.1111/j.1463-5224.2006.00463.x PubMedCrossRefGoogle Scholar
  2. 2.
    Barnett KC, Heywood R, Hague PH (1972) Colloid degeneration of the retina in a baboon. J Comp Pathol 82:117–118, doi: 10.1016/0021-9975(72)90052-7 PubMedCrossRefGoogle Scholar
  3. 3.
    Bellhorn RW, King CD, Aguirre GD, Ripps H, Siegel IM, Tsai HC (1981) Pigmentary abnormalities of the macula in rhesus monkeys: clinical observations. Invest Ophthalmol Vis Sci 21:771–781PubMedGoogle Scholar
  4. 4.
    Dastgheib K, Green W (1994) Granulomatous reaction to Bruch’s membrane in age-related macular degeneration. Arch Ophthalmol 112:813–818PubMedGoogle Scholar
  5. 5.
    El Mofty AAM, Gouras P, Eisner G, Balazs EA (1978) Macular degeneration in rhesus monkeys (Macaca mulatta). Exp Eye Res 27:499–502, doi: 10.1016/0014-4835(78)90027-1 PubMedCrossRefGoogle Scholar
  6. 6.
    El Mofty AAM, Eisner G, Balazs EA, Denlinger JL, Gouras P (1980) Retinal degeneration in rhesus monkeys, Macaca mulatta. Survey of three seminatural free-breeding colonies. Exp Eye Res 31:147–166, doi: 10.1016/0014-4835(80)90075-5 PubMedCrossRefGoogle Scholar
  7. 7.
    Feeney-Burns L, Malinow R, Klein ML, Neuringer M (1981) Maculopathy in cynomolgous monkeys. A correlated fluorescein angiographic and ultrastructural study. Arch Ophthalmol 99:664–672PubMedGoogle Scholar
  8. 8.
    Fine BS, Kwapien RP (1978) Pigment and epithelial windows and drusen: an animal model. Invest Ophthalmol Vis Sci 17:1059–1068PubMedGoogle Scholar
  9. 9.
    Gouras P, Ivert L, Mattison J, Neuringer M (submitted) Autofluorescence, lipofuscin and the pathogenesis of drusen in rhesus monkeysGoogle Scholar
  10. 10.
    Green WR, Key SN 3rd (1977) Senile macular degeneration: a histopathologic study. Trans Am Ophthalmol Soc 75:180–254PubMedGoogle Scholar
  11. 11.
    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
  12. 12.
    Hope GM, Dawson WW, Engel HM, Ulshafer RJ, Kessler MJ, Sherwood MB (1992) A primate model for age related macular drusen. Br J Ophthalmol 76:11–16, doi: 10.1136/bjo.76.1.11 PubMedCrossRefGoogle Scholar
  13. 13.
    Ingram DK, Cutler RG, Weindruch R, Renquist DM, Knapka JJ, April M et al (1990) Dietary restriction and aging: initiation of a primate study. J Gerontol 45:B148–B163PubMedGoogle Scholar
  14. 14.
    Ishibashi T, Sorgente N, Patterson R, Ryan S (1986) Pathogenesis of drusen in the primate. Invest Ophthalmol Vis Sci 27:184–193PubMedGoogle Scholar
  15. 15.
    Killingsworth M, Sarks J, Sarks S (1990) Macrophages related to Bruch’s membrane in age-related macular degeneration. Eye 4:613–621PubMedGoogle Scholar
  16. 16.
    Lowenstein A, Bressler NM, Bressler SB (1998) Epidemiology of age-related retinal pigment epithelial disease. In: Marmor MF, Wolfensberger TJ (eds) The retinal pigment epithelium. Oxford University Press, New York, pp 716–725Google Scholar
  17. 17.
    Mattison JA, Roth GS, Lane MA, Ingram DK (2007) Dietary restriction in aging non-human primates. Interdiscip Top Gerontol 35:137–158PubMedGoogle Scholar
  18. 18.
    Monaco WA, Wormington CM (1990) The rhesus monkey as an animal model for age-related maculopathy. Optom Vis Sci 67:532–537, doi: 10.1097/00006324-199007000-00011 PubMedCrossRefGoogle Scholar
  19. 19.
    Mullins RF, Hageman GS (1997) Histochemical comparison of ocular “drusen” in monkey and human. In: LaVail MM, Hollyfield JG, Anderson RE (eds) Degenerative retinal diseases. Plenum Press, New York, pp 1–24Google Scholar
  20. 20.
    Penfold P, Killingsworth M, Sarks S (1985) Senile macular degeneration: the involvement of immunocompetent cells. Graefes Arch Clin Exp Ophthalmol 223:69–76, doi: 10.1007/BF02150948 PubMedCrossRefGoogle Scholar
  21. 21.
    Roth GS, Mattison JA, Ottinger MA, Chachich ME, Lane MA, Ingram DK (2004) Aging in rhesus monkeys: relevance to human health interventions. Science 305:1423–1426, doi: 10.1126/science.1102541 PubMedCrossRefGoogle Scholar
  22. 22.
    Rubin LF (1974) The monkey fundus In: Atlas of veterinary ophthalmology. Lea & Febiger, Philadelphia, pp 399–449Google Scholar
  23. 23.
    Sarks S (1980) Drusen and their relationship to senile macular degeneration. Aust J Ophthalmol 8:117–130, doi: 10.1111/j.1442-9071.1980.tb01670.x PubMedCrossRefGoogle Scholar
  24. 24.
    Sinclair DA (2005) Toward a unified theory of caloric restriction and longevity regulation. Mech Ageing Dev 126:987–1002, doi: 10.1016/j.mad.2005.03.019 PubMedCrossRefGoogle Scholar
  25. 25.
    Stafford TJ (1974) Maculopathy in an elderly subhuman primate. In: Streiff EB (ed) Modern problems in ophthalmology Vol 12 Limitations and prospects for retinal surgery. Karger, Miami, pp 214–219Google Scholar
  26. 26.
    Stafford TJ, Anness SH, Fine BS (1984) Spontaneous degenerative maculopathy in the monkey. Ophthalmol 91:513–521Google Scholar
  27. 27.
    Ulshafer RJ, Engel HM, Dawson WW, Allen CB, Kessler MJ (1987) Macular degeneration in a community of rhesus monkeys. Retina 7:198–203, doi: 10.1097/00006982-198700730-00011 PubMedCrossRefGoogle Scholar
  28. 28.
    Umeda S, Suzuki MT, Okamoto H, Ono F, Mizota A, Terao K et al (2005) Molecular composition of drusen and possible involvement of anti-retinal autoimmunity in two different forms of macular degeneration in cynomolgus monkey (Macaca fasicularis). FASEB J 12:1683–1685Google Scholar
  29. 29.
    Umeda S, Ayyagari R, Allikmets R, Suzuki MT, Karoukis AJ, Ambasudhan R et al (2005) Early-onset macular degeneration with drusen in a cynomolgous monkey (Macaca fascicularis) pedigree: exclusion of 13 candidate genes. Invest Ophthalmol Vis Sci 46:683–691, doi: 10.1167/iovs.04-1031 PubMedCrossRefGoogle Scholar
  30. 30.
    Vainisi SJ, Beck BB, Apple DJ (1971) Retinal degeneration in baboon. Am J Ophthalmol 78:279–284Google Scholar
  31. 31.
    Vinding T (1995) Age-related macular degeneration. An epidemiological study of 1000 elderly individuals with reference to prevalence, funduscopic findings, visual impairment and risk factors. Acta Ophthalmol Scand Suppl 217:1–32PubMedGoogle Scholar
  32. 32.
    Vingerling J, Dielmans I, Hofman A (1995) The prevalence of age-related maculopathy in the Rotterdam Study. Ophthalmology 102:205–210PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

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

Personalised recommendations