Complement Activation of Drusen in Primate Model (Macaca fascicularis) for Age-Related Macular Degeneration

  • Takeshi Iwata
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 598)


Macular Degeneration Choroidal Neovascularization Membrane Cofactor Protein Macaca Fascicularis Retinal Pigment Epithelial Cell Layer 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Ambati, J., Anand, A., Fernandez, S., Sakurai, E., Lynn, B. C., Kuziel, W. A., Rollins, B. J., Ambati, B. K. (2003) An animal model of age-related macular degeneration in senescent Ccl-2- or Ccr-2-deficient mice. Nat. Med. 9,1390-1397.PubMedCrossRefGoogle Scholar
  2. Chader, G. J. (2002) Animal models in research on retinal degenerations: Past progress and future hope. Vision Res 42,393-399.PubMedCrossRefGoogle Scholar
  3. Dewan A., Liu, M., Hartman, S., Zhang, S. S., Liu, D. T., Zhao, C., Tam, P. O., Chan, W. M., Lam, D. S., Snyder, M., Barnstable, C., Pang, C. P., Hoh, J. (2006) HTRA1 promoter polymorphism in wet age-related macular degeneration. Science 314,989-992.PubMedCrossRefGoogle Scholar
  4. Edwards, A. O., Ritter, R. 3rd., Abel, K. J., Manning, A., Panhuysen, C., Farrer, L. A. (2005) Complement factor H polymorphism and age-related macular degeneration. Science 308,421-424.PubMedCrossRefGoogle Scholar
  5. El-Mofty A., Gouras, P., Eisner, G., Balazs, E. A. (1978) Macular degeneration in rhesus monkey (Macaca mulatta). Exp. Eye Res. 27,499-502.PubMedCrossRefGoogle Scholar
  6. Gold, B., Merriam, J. E., Zernant, J., Hancox, L. S., Taiber, A. J., Gehrs, K., Cramer, K., Neel, J., Bergeron, J., Barile, G. R., Smith, R. T. (2006) AMD Genetics Clinical Study Group; G. S. Hageman, M. Dean, R. Allikmets. Variation in factor B (BF) and complement component 2 (C2) genes is associated with age-related macular degeneration. Nat. Genet. 38,458-462.Google Scholar
  7. Gotoh, N., Yamada, R., Hiratani, H., Renault, V., Kuroiwa, S., Monet, M., Toyoda, S., Chida, S., Mandai, M., Otani, A., Yoshimura, N., Matsuda, F. (2006) No association between complement factor H gene polymorphism and exudative age-related macular degeneration in Japanese. Hum. Genet. 120, 139-143.PubMedCrossRefGoogle Scholar
  8. Hageman, G. S., Anderson, D. H., Johnson, L. V., Hancox, L. S., Taiber, A. J., Hardisty, L. I., Hageman, J. L., Stockman, H. A., Borchardt, J. D., Gehrs, K. M., Smith, R. J., Silvestri, G., Russell, S. R., Klaver, C. C., Barbazetto, I., Chang, S., Yannuzzi, L. A., Barile, G. R., Merriam, J. C., Smith, R. T., Olsh, A. K., Bergeron, J., Zernant, J., Merriam, J. E., Gold, B., Dean, M., Allikmets, R. (2005) A common haplotype in the complement regulatory gene factor H (HF1/CFH) predisposes individuals to age-related macular degeneration. Proc. Natl. Acad. Sci. U S A 102,7227-7232.PubMedCrossRefGoogle Scholar
  9. Haines, J. L., Hauser, M. A., Schmidt, S., Scott, W. K., Olson, L. M., Gallins, P., Spencer, K. L., Kwan, S. Y., Noureddine, M., Gilbert, J. R., Schnetz-Boutaud, N., Agarwal, A., Postel, E. A., Pericak-Vance, M. A. (2005) Complement factor H variant increases the risk of age-related macular degeneration. Science 308,419-421.PubMedCrossRefGoogle Scholar
  10. Hammond, C. J., Webster, A. R., Snieder, H., Bird, A. C., Gilbert, C. E., Spector, T. D. (2002) Genetic influence on early age-related maculopathy: A twin study. Ophthalmology 109,730-736.PubMedCrossRefGoogle Scholar
  11. Heiba, I. M., Elston, R. C., Klein, B. E., Klein, R. (1994) Sibling correlations and segregation analysis of age-related maculopathy: The Beaver Dam Eye Study. Genet. Epidemiol. 11,51-67.PubMedCrossRefGoogle Scholar
  12. Imamura, Y., Noda, S., Hashizume, K., Shinoda, K., Yamaguchi, M., Uchiyama, S., Shimizu, T., Mizushima, Y., Shirasawa, T., Tsubota, K. (2006) Drusen, choroidal neovascularization, and retinal pigment epithelium dysfunction in SOD1-deficient mice: a model of age-related macular degeneration. Proc Natl Acad Sci U S A 103,11282-11287.PubMedCrossRefGoogle Scholar
  13. Iyengar, S. K., Song, D., Klein, B. E., Klein, R., Schick, J. H., Humphrey, J., Millard, C., Liptak, R., Russo, K., Jun, G., Lee, K. E., Fijal, B., Elston, R. C. (2004) Dissection of genomewide-scan data in extended families reveals a major locus and oligogenic susceptibility for age-related macular degeneration. Am. J. Hum. Genet. 74,20-39.PubMedCrossRefGoogle Scholar
  14. Klein, R. J., Zeiss, C., Chew, E. Y., Tsai, J. Y., Sackler, R. S., Haynes, C., Henning, A. K., SanGiovanni, J. P., Mane, S. M., Mayne, S. T., Bracken, M. B., Ferris, F. L., Ott, J., Barnstable, C., Hoh, J. (2005) Complement factor H polymorphism in age-related macular degeneration. Science 308,385-389.PubMedCrossRefGoogle Scholar
  15. Schick, J. H., Iyengar, S. K., Klein, B. E., Klein, R., Reading, K., Liptak, R., Millard, C., Lee, K. E., Tomany, S. C., Moore, E. L., Fijal, B. A., Elston, R. C. (2003) A whole-genome screen of a quantitative trait of age-related maculopathy in sibships from the Beaver Dam Eye Study. Am. J. Hum. Genet. 72,1412-1424.PubMedCrossRefGoogle Scholar
  16. Majewski, J., Schultz, D. W., Weleber, R. G., Schain, M. B., Edwards, A. O., Matise, T. C., Acott, T. S., Ott, J., Klein, M. L. (2003) Age-related macular degeneration–a genome scan in extended families. Am. J. Hum. Genet. 73,540-550.PubMedCrossRefGoogle Scholar
  17. Malek, G., Johnson, L. V., Mace, B. E., Saloupis, P., Schmechel, D. E., Rickman, D. W., Toth, C. A., Sullivan, P. M., Bowes Rickman, C. (2005) Apolipoprotein E allele-dependent pathogenesis: a model for age-related retinal degeneration. Proc. Natl. Acad. Sci. U S A. 102,11900-11905.PubMedCrossRefGoogle Scholar
  18. Mullins, R. F., Russell, S. R., Anderson, D. H., Hageman, G. S. (2000) Drusen associated with aging and age-related macular degeneration contain proteins common to extracellular deposits associated with atherosclerosis, elastosis, amyloidosis, and dense deposit disease. FASEB J 14,835-846.PubMedGoogle Scholar
  19. Nicolas, M. G., Fujiki, K., Murayama, K., Suzuki, M. T., Mineki, R., Hayakawa, M., Yoshikawa, Y., Cho, F., Kanai, A. (1996) Studies on the mechanism of early onset macular degeneration in cynomolgus (Macaca fascicularis) monkeys. I. Abnormal concentrations of two proteins in the retina. Exp. Eye Res. 62,211-219.PubMedCrossRefGoogle Scholar
  20. Nicolas, M. G., Fujiki, K., Murayama, K., Suzuki, M. T., Shindo, N., Hotta, Y., Iwata, F., Fujimura, T., Yoshikawa, Y., Cho, F., Kanai, (1996) A. Studies on the mechanism of early onset macular degeneration in cynomolgus monkeys. II. Suppression of metallothionein synthesis in the retina in oxidative stress. Exp. Eye Res. 62,399-408.PubMedCrossRefGoogle Scholar
  21. Nozaki, M., Raisler, B. J., Sakurai, E., Sarma, J. V., Barnum, S. R., Lambris, J. D., Chen, Y., Zhang, K., Ambati, B. K., Baffi, J. Z., Ambati J. (2006) Drusen complement components C3a and C5a promote choroidal neovascularization. Proc. Natl. Acad. Sci. U S A 103,2328-2333.PubMedCrossRefGoogle Scholar
  22. Okamoto, H., Umeda, S., Obazawa, M., Minami, M., Noda, T., Mizota, A., Honda, M., Tanaka, M., Koyama, R., Takagi, I., Sakamoto, Y., Saito, Y., Miyake, Y., Iwata, T. (2006) Complement factor H polymorphisms in Japanese population with age-related macular degeneration. Mol. Vis. 12,156-158.PubMedGoogle Scholar
  23. Russell, S. R., Mullins, R. F., Schneider, B. L., Hageman, G. S. (2000) Location, substructure, and composition of basal laminar drusen compared with drusen associated with aging and age-related macular degeneration. Am J Ophthalmol 129,205-214.PubMedCrossRefGoogle Scholar
  24. Seddon, J. M., Ajani, U. A., Mitchell, B. D. (1997) Familial aggregation of age-related maculopathy. Am. J. Ophthalmology 123,199-206.Google Scholar
  25. Stafford, T. J., Anness, S. H., Fine, B. S. (1984) Spontaneous degenerative maculopathy in the monkey. Ophthalmology 91,513-521.PubMedGoogle Scholar
  26. Yang, Z., Camp, N. J., Sun, H., Tong, Z., Gibbs, D., Cameron, D. J., Chen, H., Zhao, Y., Pearson, E., Li, X., Chien, J., Dewan, A., Harmon, J., Bernstein, P. S., Shridhar, V., Zabriskie, N. A., Hoh, J., Howes, K., Zhang, K.. (2006) A variant of the HTRA1 gene increases susceptibility to age-related macular degeneration. Science. 314,992-993.PubMedCrossRefGoogle Scholar
  27. Yoshida, T., Dewan, A., Zhang, H., Sakamoto, R., Okamoto, H., Minami, M., Obazawa, M., Mizota, A., Tanaka, M., Saito, Y., Takagi, I., Hoh, J., Iwatra, T. (2007) HTRA1 promoter polymorphism predisposes Japanese to age-related macular degeneration. Mol. Vis. 4, 13:545-548.Google Scholar
  28. Umeda, S., Ayyagari, R., Allikmets, R., Suzuki, M. T., Karoukis, A. J., Ambasudhan, R., Zernant, J., Okamoto, H., Ono, F., Terao, K., Mizota, A., Yoshikawa, Y., Tanaka, Y., Iwata, T. (2005) Early-onset macular degeneration with drusen in a cynomolgus monkey (Macaca fascicularis) pedigree: exclusion of 13 candidate genes and loci. Invest. Ophthalmol. Vis. Sci. 46,683-691.PubMedCrossRefGoogle Scholar
  29. Umeda, S., Suzuki, M. T., Okamoto, H., Ono, F., Mizota, A., Terao, K., Yoshikawa, Y., Tanaka, Y., Iwata, T. (2005) Molecular composition of drusen and possible involvement of anti-retinal autoimmunity in two different forms of macular degeneration in cynomolgus monkey (Macaca fascicularis). FASEB J. 19,1683-1685.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Takeshi Iwata
    • 1
  1. 1.National Institute of Sensory Organs, National Hospital OrganizationTokyo Medical CenterTokyo 152-8902Japan

Personalised recommendations