Skip to main content

Carboxyethylpyrrole Adducts, Age-related Macular Degeneration and Neovascularization

  • Chapter

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 613))

Choroidal neovascularization (CNV) in late stage age-related macular degeneration (AMD) involves abnormal vessel growth from the choriocapillaris through Bruch’s membrane and the retinal pigment epithelium (RPE) and accounts for more than 80%of the severe debilitating vision loss in all AMD patients. The molecular mechanisms associated with AMD pathogenesis and the development of CNV remain poorly understood.We hypothesize that oxidative protein modifications are primary catalysts in AMD pathogenesis and play a role in the development of CNV (Crabb et al., 2002). Oxidative damage has long been suspected of contributing to AMD (Beatty et al., 2000), supported by indirect evidence that smoking increases the risk of AMD (Seddon et al., 1996) and that antioxidant vitamins and zinc can slow disease progression for select individuals (AREDS, 2001).

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • AREDS (2001). “A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins c and e, beta carotene, and zinc for age-related macular degeneration and vision loss: Areds report no. 8.” Arch Ophthalmol 119: 1417.

    Google Scholar 

  • Beatty, S., H. Koh, M. Phil, D. Henson and M. Boulton (2000). “The role of oxidative stress in the pathogenesis of age-related macular degeneration.” Surv Ophthalmol 45: 115.

    Article  PubMed  CAS  Google Scholar 

  • Crabb, J. W., M. Miyagi, X. Gu, K. Shadrach, K. A. West, H. Sakaguchi, M. Kamei, A. Hasan, L. Yan, M. E. Rayborn, R. G. Salomon and J. G. Hollyfield (2002). “Drusen proteome analysis: An approach to the etiology of age-related macular degeneration.” Proc Natl Acad Sci U S A 99: 14682.

    Article  PubMed  CAS  Google Scholar 

  • Dewan, A., M. Liu, S. Hartman, S. S. Zhang, D. T. Liu, C. Zhao, P. O. Tam, W. M. Chan, D. S. Lam, M. Snyder, C. Barnstable, C. P. Pang and J. Hoh (2006). “Htra1 promoter polymorphism in wet age-related macular degeneration.” Science 314: 989.

    Article  PubMed  CAS  Google Scholar 

  • Ebrahem, Q., K. Renganathan, J. Sears, A. Vasanji, X. Gu, L. Lu, R. G. Salomon, J. W. Crabb and B. Anand-Apte (2006). “Carboxyethylpyrrole oxidative protein modifications stimulate neovascularization: Implications for age-related macular degeneration.” Proc Natl Acad Sci U S A 103: 13480.

    Article  PubMed  CAS  Google Scholar 

  • Edwards, A. O., R. Ritter, 3rd, K. J. Abel, A. Manning, C. Panhuysen and L. A. Farrer (2005). “Complement factor h polymorphism and age-related macular degeneration.” Science 308: 421.

    Article  PubMed  CAS  Google Scholar 

  • Fliesler, S. J. and R. E. Anderson (1983). “Chemistry and metabolism of lipids in the vertebrate retina.” Prog Lipid Res 22: 79.

    Article  PubMed  CAS  Google Scholar 

  • Gold, B., J. E. Merriam, J. Zernant, L. S. Hancox, A. J. Taiber, K. Gehrs, K. Cramer, J. Neel, J. Bergeron, G. R. Barile, R. T. Smith, G. S. Hageman, M. Dean and R. Allikmets (2006). “Variation in factor b (bf) and complement component 2 (c2) genes is associated with age-related macular degeneration.” Nat Genet 38: 458.

    Article  PubMed  CAS  Google Scholar 

  • Gragoudas, E. S., A. P. Adamis, E. T. Cunningham, Jr., M. Feinsod and D. R. Guyer (2004). “Pegaptanib for neovascular age-related macular degeneration.” N Engl J Med 351: 2805.

    Article  PubMed  CAS  Google Scholar 

  • Gu, X., S. G. Meer, M. Miyagi, M. Rayborn, J. G. Hollyfield, J. W. Crabb and R. G. Salomon (2003). “Carboxyethylpyrrole proein adducts and autoantibodies, biomarkers for age-related macular degeneration.” J. Biol. Chem. 278: 42027.

    Article  PubMed  CAS  Google Scholar 

  • Hageman, G. S., D. H. Anderson, L. V. Johnson, L. S. Hancox, A. J. Taiber, L. I. Hardisty, J. L. Hageman, H. A. Stockman, J. D. Borchardt, K. M. Gehrs, R. J. Smith, G. Silvestri, S. R. Russell, C. C. Klaver, I. Barbazetto, S. Chang, L. A. Yannuzzi, G. R. Barile, J. C. Merriam, R. T. Smith, A. K. Olsh, J. Bergeron, J. Zernant, J. E. Merriam, B. Gold, M. Dean and R. Allikmets (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.

    Article  PubMed  CAS  Google Scholar 

  • Haines, J. L., M. A. Hauser, S. Schmidt, W. K. Scott, L. M. Olson, P. Gallins, K. L. Spencer, S. Y. Kwan, M. Noureddine, J. R. Gilbert, N. Schnetz-Boutaud, A. Agarwal, E. A. Postel and M. A. Pericak-Vance (2005). “Complement factor h variant increases the risk of age-related macular degeneration.” Science 308: 419.

    Article  PubMed  CAS  Google Scholar 

  • Handa, J. T., N. Verzijl, H. Matsunaga, A. Aotaki-Keen, G. A. Lutty, J. M. te Koppele, T. Miyata and L. M. Hjelmeland (1999). “Increase in the advanced glycation end product pentosidine in bruch’s membrane with age.” Invest Ophthalmol Vis Sci 40: 775.

    PubMed  CAS  Google Scholar 

  • Hirata, C., K. Nakano, N. Nakamura, Y. Kitagawa, H. Shigeta, G. Hasegawa, M. Ogata, T. Ikeda, H. Sawa, K. Nakamura, K. Ienaga, H. Obayashi and M. Kondo (1997). “Advanced glycation end products induce expression of vascular endothelial growth factor by retinal muller cells.” Biochem Biophys Res Commun 236: 712.

    Article  PubMed  CAS  Google Scholar 

  • Hoffmann, S., R. Masood, Y. Zhang, S. He, S. J. Ryan, P. Gill and D. R. Hinton (2000). “Selective killing of rpe with a vascular endothelial growth factor chimeric toxin.” Invest Ophthalmol Vis Sci 41: 2389.

    PubMed  CAS  Google Scholar 

  • Imamura, Y., S. Noda, K. Hashizume, K. Shinoda, M. Yamaguchi, S. Uchiyama, T. Shimizu, Y. Mizushima, T. Shirasawa and K. Tsubota (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.

    Article  PubMed  CAS  Google Scholar 

  • Ishibashi, T., T. Murata, M. Hangai, R. Nagai, S. Horiuchi, P. F. Lopez, D. R. Hinton and S. J. Ryan (1998). “Advanced glycation end products in age-related macular degeneration.” Arch Ophthalmol 116: 1629.

    PubMed  CAS  Google Scholar 

  • Jakobsdottir, J., Y. P. Conley, D. E. Weeks, T. S. Mah, R. E. Ferrell and M. B. Gorin (2005). “Susceptibility genes for age-related maculopathy on chromosome 10q26.” Am J Hum Genet 77: 389.

    Article  PubMed  CAS  Google Scholar 

  • Klein, R. J., C. Zeiss, E. Y. Chew, J. Y. Tsai, R. S. Sackler, C. Haynes, A. K. Henning, J. P. SanGiovanni, S. M. Mane, S. T. Mayne, M. B. Bracken, F. L. Ferris, J. Ott, C. Barnstable and J. Hoh (2005). “Complement factor h polymorphism in age-related macular degeneration.” Science 308: 385.

    Article  PubMed  CAS  Google Scholar 

  • Lewin, A. S., V. Justilien, J. Pang, W. W. Hauswirth, J. W. Crabb, N. Renganathan, S. R. Kim and J. R. Sparrow (2007). “Modeling early stages of age-related macular degeneration (amd) by inducing oxidative stress in the rpe ” Invest Opthalmol Vis Sci, E-abstract 5055.

    Google Scholar 

  • Malek, G., L. V. Johnson, B. E. Mace, P. Saloupis, D. E. Schmechel, D. W. Rickman, C. A. Toth, P. M. Sullivan and C. B. Rickman (2005). “Apolipoprotein e allele-dependent pathogenesis: A model for age-related retinal degeneration.” Proc Natl Acad Sci U S A 102: 11900.

    Article  PubMed  CAS  Google Scholar 

  • Okamoto, T., S. Tanaka, A. C. Stan, T. Koike, M. Kase, Z. Makita, H. Sawa and K. Nagashima (2002). “Advanced glycation end products induce angiogenesis in vivo.” Microvasc Res 63: 186.

    Article  PubMed  CAS  Google Scholar 

  • Rivera, A., S. A. Fisher, L. G. Fritsche, C. N. Keilhauer, P. Lichtner, T. Meitinger and B. H. Weber (2005). “Hypothetical loc387715 is a second major susceptibility gene for age-related macular degeneration, contributing independently of complement factor h to disease risk.” Hum Mol Genet 14: 3227.

    Article  PubMed  CAS  Google Scholar 

  • Rosenfeld, P. J., S. D. Schwartz, M. S. Blumenkranz, J. W. Miller, J. A. Haller, J. D. Reimann, W. L. Greene and N. Shams (2005). “Maximum tolerated dose of a humanized anti-vascular endothelial growth factor antibody fragment for treating neovascular age-related macular degeneration.” Ophthalmology 112: 1048.

    Article  PubMed  Google Scholar 

  • Seddon, J. M., W. C. Willett, F. E. Speizer and S. E. Hankinson (1996). “A prospective study of cigarette smoking and age-related macular degeneration in women.” J Am Med Assoc 276: 1141.

    Article  CAS  Google Scholar 

  • Wu, J. T. (1993). “Advanced glycosylation end products: A new disease marker for diabetes and aging.” J Clin Lab Anal 7: 252.

    Article  PubMed  CAS  Google Scholar 

  • Yang, Z., N. J. Camp, H. Sun, Z. Tong, D. Gibbs, D. J. Cameron, H. Chen, Y. Zhao, E. Pearson, X. Li, J. Chien, A. Dewan, J. Harmon, P. S. Bernstein, V. Shridhar, N. A. Zabriskie, J. Hoh, K. Howes and K. Zhang (2006). “A variant of the htra1 gene increases susceptibility to age-related macular degeneration.” Science 314: 992.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2008 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Renganathan, K. et al. (2008). Carboxyethylpyrrole Adducts, Age-related Macular Degeneration and Neovascularization. In: Anderson, R.E., LaVail, M.M., Hollyfield, J.G. (eds) Recent Advances in Retinal Degeneration. Advances in Experimental Medicine and Biology, vol 613. Springer, New York, NY. https://doi.org/10.1007/978-0-387-74904-4_30

Download citation

  • DOI: https://doi.org/10.1007/978-0-387-74904-4_30

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-0-387-74902-0

  • Online ISBN: 978-0-387-74904-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics