Skip to main content
SpringerLink
Log in

Inflammatory Biomarkers for AMD

  • Conference paper
  • First Online:
Retinal Degenerative Diseases

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 801))

Abstract

Age-related macular degeneration (AMD) is the leading cause of blindness worldwide, affecting an estimated 50 million individuals aged over 65 years.

Environmental and genetic risk-factors implicate chronic inflammation in the etiology of AMD, contributing to the formation of drusen, retinal pigment epithelial cell dysfunction and photoreceptor cell death. Consistent with a role for chronic inflammation in AMD pathogenesis, several inflammatory mediators, including complement components, chemokines and cytokines, are elevated at both the local and systemic levels in AMD patients. These mediators have diverse roles in the alternative complement pathway, including recruitment of inflammatory cells, activation of the inflammasome, promotion of neovascularisation and in the resolution of inflammation. The utility of inflammatory biomarkers in assessing individual risk and progression of the disease is controversial. However, understanding the role of these inflammatory mediators in AMD onset, progression and response to treatment may increase our knowledge of disease pathogenesis and provide novel therapeutic options in the future.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 259.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
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

Institutional subscriptions

Abbreviations

AMD:

Age-related macular degeneration

RPE:

Retinal pigment epithelial

CNV:

Choroidal neovascularisation

VEGF:

Vascular endothelial growth factor

CRP:

C-reactive protein

A2E:

N-retinylidene-N retinylethanolamine

CEP:

Carboxyethylpyrrole

NLRP3:

NACHT, LRR and PYD domains-containing protein 3

CFH:

Complement factor H

CFD:

Complement factor D

CCL2:

Chemokine, CC motif, ligand 2

CCR2:

Chemokine, CC motif, receptor type 2

IL-6:

Interleukin-6

References

  1. Friedman D, O’Colmain B, Munoz B, Tomany S, McCarty C, Jong P et al (2004) Prevalence of age-related macular degeneration in the United States. Arch Ophthalmol 122(4):564–572

    Article  PubMed  Google Scholar 

  2. Anderson DH, Mullins RF, Hageman GS, Johnson LV (2002) A role for local inflammation in the formation of drusen in the aging eye. Am J Ophthalmol 134(3):411–431

    Article  PubMed  CAS  Google Scholar 

  3. Crabb JW, Miyagi M, Gu X, Shadrach K, West KA, Sakaguchi H et al (2002) Drusen proteome analysis: an approach to the etiology of age-related macular degeneration. Proc Natl Acad Sci USA 99(23):14682–14687

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  4. Hageman GS, Luthert PJ, Victor Chong NH, 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 in aging and age-related macular degeneration. Prog Retin Eye Res 20(6):705–732

    Article  PubMed  CAS  Google Scholar 

  5. Zhou J, Jang YP, Kim SR, Sparrow JR (2006) Complement activation by photooxidation products of A2E, a lipofuscin constituent of the retinal pigment epithelium. Proc Natl Acad Sci USA 103(44):16182–16187

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  6. Johnson LV, Leitner WP, Rivest AJ, Staples MK, Radeke MJ, Anderson DH (2002) The Alzheimer’s Aβ-peptide is deposited at sites of complement activation in pathologic deposits associated with aging and age-related macular degeneration. Proc Natl Acad Sci USA 99(18):11830–11835

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  7. Hollyfield JG, Bonilha VL, Rayborn ME, Yang X, Shadrach KG, Lu L et al (2008) Oxidative damage-induced inflammation initiates age-related macular degeneration. Nat Med 14(2):194–198

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  8. Doyle SL, Campbell M, Ozaki E, Salomon RG, Mori A, Kenna PF et al (2012) NLRP3 has a protective role in age-related macular degeneration through the induction of IL-18 by drusen components. Nat Med 18(5):791–798

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  9. Edwards AO, Ritter R, Abel KJ, Manning A, Panhuysen C Farrer LA (2005) Complement factor H polymorphism and age-related macular degeneration. Science 308(5720):421–424

    Article  PubMed  CAS  Google Scholar 

  10. Hageman GS, Anderson DH, Johnson LV, Hancox LS, Taiber AJ, Hardisty LI et al (2005) A common haplotype in the complement regulatory gene factor H (HF1/CFH) predisposes individuals to age-related macular degeneration. Proc Natl Acad Sci USA 102(20):7227–7232

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  11. Haines JL, Hauser M, Schmidt S, Scott WK, Olson LM, Gallins P et al (2005) Complement factor H variant increases the risk of age-related macular degeneration. Science 308:419–421

    Article  PubMed  CAS  Google Scholar 

  12. Gold B, Merriam JE, Zernant J, Hancox LS, Taiber AJ, Gehrs K et al (2006) Variation in factor B (BF) and complement component 2 (C2) genes is associated with age-related macular degeneration. Nat Genet 38(4):458–462

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  13. Yates JRW, Sepp T, Matharu BK, Khan JC, Thurlby DA, Shahid H et al (2007) Complement C3 Variant and the Risk of Age-Related Macular Degeneration. N Engl J Med 357(6):553–561

    Article  PubMed  CAS  Google Scholar 

  14. Heurich M, Martínez-Barricarte R, Francis NJ, Roberts DL, Rodríguez deCS, Morgan BP et al (2011) Common polymorphisms in C3, factor B, and factor H collaborate to determine systemic complement activity and disease risk. Proc Natl Acad Sci USA 108(21):8761–8766

    Article  PubMed Central  PubMed  Google Scholar 

  15. Hecker LA, Edwards AO, Ryu E, Tosakulwong N, Baratz KH, Brown WL et al (2010) Genetic control of the alternative pathway of complement in humans and age-related macular degeneration. Hum Mol Genet 19(1):209–215

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  16. Reynolds R, Hartnett ME, Atkinson JP, Giclas PC, Rosner B, Seddon JM (2009) Plasma complement components and activation fragments: associations with age-related macular degeneration genotypes and phenotypes. Invest Ophthalmol Vis Sci 50(12):5818–5827

    Article  PubMed Central  PubMed  Google Scholar 

  17. Scholl HPN, Issa PC, Walier M, Janzer S, Pollok-kopp B, Fritsche LG et al (2008) Systemic Complement Activation in Age-Related Macular Degeneration. PLoS One 3(7):e2593

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  18. Stanton CM, Yates JRW, den Hollander AI, Seddon JM, Swaroop A, Stambolian D et al (2011) Complement Factor D in Age-Related Macular Degeneration. Invest Ophthalmol Vis Sci 52(12):8828–8834

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  19. Seddon J, Gensler G, Milton R, Klein M, Rifai N (2004) Association between c-reactive protein and age-related macular degeneration. JAMA 291(6):704–710

    Article  PubMed  CAS  Google Scholar 

  20. Seddon JM, Gensler G, Rosner B (2010) C-Reactive Protein and CFH ARMS2/HTRA1 Gene Variants Are Independently Associated with Risk of Macular Degeneration. Ophthalmology 117(8):1560–1566

    Article  PubMed Central  PubMed  Google Scholar 

  21. Vine AK, Stader J, Branham K, Musch DC, Swaroop A (2005) Biomarkers of Cardiovascular Disease as Risk Factors for Age-Related Macular Degeneration. Ophthalmology 112(12):2076–2080

    Article  PubMed  Google Scholar 

  22. Dasch B, Fuhs A, Behrens T, Meister A, Wellmann J, Fobker M et al (2005) Inflammatory markers in age-related maculopathy: Cross-sectional analysis from the muenster aging and retina study. Arch Ophthalmol 123(11):1501–1506

    Article  PubMed  CAS  Google Scholar 

  23. Klein R, Klein BEK, Knudtson MD, Wong TY, Shankar A, Tsai MY (2005) Systemic markers of inflammation, endothelial dysfunction, and age-related maculopathy. Am J Ophthalmol 140(1):35–44

    PubMed  CAS  Google Scholar 

  24. McGwin G, Hall TA, Xie A, Owsley C (2005) The relation between C reactive protein and age related macular degeneration in the cardiovascular health study. Br J Ophthalmol 89(9):1166–1170

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  25. Seddon J, George S, Rosner B, Rifai N (2005) Progression of age-related macular degeneration: Prospective assessment of c-reactive protein, interleukin 6, and other cardiovascular biomarkers. Arch Ophthalmol 123(6):774–782

    Article  PubMed  Google Scholar 

  26. Langmann T (2007) Microglia activation in retinal degeneration. J Leukoc Biol 81(6):1345–1351

    Article  PubMed  CAS  Google Scholar 

  27. Forrester JV (2003) Macrophages eyed in macular degeneration. Nat Med 9(11):1350–1351

    Article  PubMed  CAS  Google Scholar 

  28. Espinosa-Heidmann DG, Suner IJ, Hernandez EP, Monroy D, Csaky KG Cousins SW (2003) Macrophage depletion diminishes lesion size and severity in experimental choroidal neovascularization. Invest Ophthalmol Vis Sci 44(8):3586–3592

    Article  PubMed  Google Scholar 

  29. Sakurai E, Anand A, Ambati BK, van Rooijen N Ambati J (2003) Macrophage depletion inhibits experimental choroidal neovascularization. Invest Ophthalmol Vis Sci 44(8):3578–3585

    Article  PubMed  Google Scholar 

  30. Leung KW, Barnstable CJ, Tombran-Tink J (2009) Bacterial endotoxin activates retinal pigment epithelial cells and induces their degeneration through IL-6 and IL-8 autocrine signaling. Mol Immunol 46(7):1374–1386

    Article  PubMed  CAS  Google Scholar 

  31. Newman A, Gallo N, Hancox L, Miller N, Radeke C, Maloney M et al (2012) Systems-level analysis of age-related macular degeneration reveals global biomarkers and phenotype-specific functional networks. Genome Med 4(2):16

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  32. Jonas J, Tao Y, Neumaier M, Findeisen P (2010) Monocyte chemoattractant protein 1, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1 in exudative age-related macular degeneration. Arch Ophthalmol 128(10):1281–1286

    Article  PubMed  CAS  Google Scholar 

  33. Mo FM, Proia AD, Johnson WH, Cyr D, Lashkari K (2010) Interferon γ-Inducible Protein-10 (IP-10) and Eotaxin as Biomarkers in Age-Related Macular Degeneration. Invest Ophthalmol Vis Sci 51(8):4226–4236

    Article  PubMed  Google Scholar 

  34. Guymer RH, Tao LW, Goh JK, Liew D, Ischenko O, Robman LD et al (2011) Identification of urinary biomarkers for age-related macular degeneration. Invest Ophthalmol Vis Sci 52(7):4639–4644

    Article  PubMed  CAS  Google Scholar 

  35. Grunin M, Burstyn-Cohen T, Hagbi-Levi S, Peled A Chowers I (2012) Chemokine receptor expression in peripheral blood monocytes from patients with neovascular age-related macular degeneration. Invest Ophthalmol Vis Sci 53(9):5292–5300

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Crewe Road, EH4 2XU, Edinburgh, UK

    Chloe M. Stanton & Alan F. Wright

Authors
  1. Chloe M. Stanton
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alan F. Wright
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Chloe M. Stanton .

Editor information

Editors and Affiliations

  1. Department of Ophthalmology, University of Florida, Gainesville, Florida, USA

    John D. Ash

  2. University Hospital Zurich, Zurich, Switzerland

    Christian Grimm

  3. Cole Eye Institute at the Cleveland Clin Division of Ophthalmology, Cleveland, Ohio, USA

    Joe G. Hollyfield

  4. Dean A. McGee Eye Inst., University of Oklahoma Health Science Center, Oklahoma City, Oklahoma, USA

    Robert E. Anderson

  5. Beckman Vision Center, University of California, San Francisco School of Medicine, San Francisco, California, USA

    Matthew M. LaVail

  6. Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina, USA

    Catherine Bowes Rickman

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media, LLC

About this paper

Cite this paper

Stanton, C., Wright, A. (2014). Inflammatory Biomarkers for AMD. In: Ash, J., Grimm, C., Hollyfield, J., Anderson, R., LaVail, M., Bowes Rickman, C. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 801. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3209-8_32

Download citation

  • DOI: https://doi.org/10.1007/978-1-4614-3209-8_32

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4614-3208-1

  • Online ISBN: 978-1-4614-3209-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation