Access

You are not currently logged in.

Access your personal account or get JSTOR access through your library or other institution:

login

Log in to your personal account or through your institution.

If You Use a Screen Reader

This content is available through Read Online (Free) program, which relies on page scans. Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.

Individuals Homozygous for the Age-related Macular Degeneration Risk-Conferring Variant of Complement Factor H Have Elevated Levels of CRP in the Choroid

P. T. Johnson, K. E. Betts, M. J. Radeke, G. S. Hageman, D. H. Anderson and L. V. Johnson
Proceedings of the National Academy of Sciences of the United States of America
Vol. 103, No. 46 (Nov. 14, 2006), pp. 17456-17461
Stable URL: http://www.jstor.org/stable/30052453
Page Count: 6
  • Read Online (Free)
  • Subscribe ($19.50)
  • Cite this Item
Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
Individuals Homozygous for the Age-related Macular Degeneration Risk-Conferring Variant of Complement Factor H Have Elevated Levels of CRP in the Choroid
Preview not available

Abstract

Polymorphisms in the complement factor H gene (CFH) are associated with a significantly increased risk for, or protection against, the development of age-related macular degeneration (AMD). The most documented risk-conferring single-nucleotide polymorphism results in a tyrosine-to-histidine substitution at position 402 (Y402H) of the CFH protein. In this work, we examined the ocular distributions and relative abundance of CFH, several CFH-binding proteins, and abundant serum proteins in the retinal pigmented epithelium (RPE), Bruch's membrane, and choroid (RPE-choroid) in CFH homozygotes possessing either the "at-risk" 402HH or "normal" 402YY variants. Although CFH immunoreactivity is high in the choroid and in drusen, no differences in CFH-labeling patterns between genotypes are apparent. In contrast, at-risk individuals have significantly higher levels of the CFH-binding protein, C-reactive protein (CRP), in the choroidal stroma. Immunoblots confirm that at-risk individuals have ≈2.5-fold higher levels of CRP in the RPE-choroid; no significant differences in the levels of CFH or other serum proteins are detected. Similarly, we find no differences in CFH transcription levels in the RPE-choroid nor evidence for local ocular CRP transcription. Increased levels of CRP in the choroid may reflect a state of chronic inflammation that is a by-product of attenuated CFH complement-inhibitory activity in those who possess the CFH at-risk allele. Because the CRP-binding site in CFH lies within the domain containing the Y402H polymorphism, it is also possible that the AMD risk-conferring allele alters the binding properties of CFH, thereby leading to choroidal CRP deposition, contributing to AMD pathogenesis.

Page Thumbnails

  • Thumbnail: Page 
17456
    17456
  • Thumbnail: Page 
17457
    17457
  • Thumbnail: Page 
17458
    17458
  • Thumbnail: Page 
17459
    17459
  • Thumbnail: Page 
17460
    17460
  • Thumbnail: Page 
17461
    17461