Skip to main content

Advertisement

Log in

Serum cytokines as biomarkers for age-related macular degeneration

  • Retinal Disorders
  • Published:
Graefe's Archive for Clinical and Experimental Ophthalmology Aims and scope Submit manuscript

Abstract

Purpose

This study evaluates the potential of serum pro-inflammatory cytokines as AMD biomarkers.

Methods

Serum samples from 30 age-related macular degeneration (AMD) patients and 15 age-matched controls were examined for 16 inflammatory cytokines using multiplex ELISA. Patients were divided into three subgroups (improvement/no change/deterioration during anti-VEGF treatment) by OCT and funduscopy, and correlated to the cytokine levels.

Results

Serum concentrations of IL-1α, IL-1β, IL-4, IL-5, IL-10, IL-13, and IL-17 were significantly higher in AMD patients than in controls. None of the co-variables expressed a significant effect on the tested cytokines. Only IL-1a and IL-17 showed a statistically significant difference between groups (improved, unchanged, deteriorated) as determined by one-way ANOVA. Patients with increased macular thickness during treatment showed significantly lower levels of IL-17 compared to improved cases and to unchanged cases (p = 0.004, 0.03 respectively, Dunnett’s T3 post hoc multiple test). TNF-α was significantly higher in improved cases compared to deteriorated cases (p =0.03, Dunnett’s T3 post hoc multiple test). IL-17 was a significant predictor for macular oedema using linear regression (β = −0.888, p <0.05).

Conclusion

Elevation of IL-1α, IL-1β, IL-4, IL-5, IL-10, IL-13, and IL-17 in the serum of AMD patients supports the hypothesis of AMD as an inflammatory disease. Patients with high IL-17 and TNF-α serum levels were more likely to have a favourable course under VEGF therapy. These cytokines may be used as easy-to-obtain biomarkers.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig.1
Fig.2

Similar content being viewed by others

References

  1. Yehoshua Z, Rosenfeld PJ, Gregori G, Penha F (2010) Spectral domain optical coherence tomography imaging of dry age-related macular degeneration. Ophthalmic Surg Lasers Imaging 41(Suppl):S6–S14

    Article  PubMed  Google Scholar 

  2. Wong TY, Wong T, Chakravarthy U, Klein R, Mitchell P, Zlateva G, Buggage R, Fahrbach K, Probst C, Sledge I (2008) The natural history and prognosis of neovascular age-related macular degeneration: a systematic review of the literature and meta-analysis. Ophthalmology 115:116–126

    Article  PubMed  Google Scholar 

  3. Ambati J, Anand A, Fernandez S, Sakurai E, Lynn BC, Kuziel WA, Rollins BJ, Ambati BK (2003) An animal model of age-related macular degeneration in senescent Ccl-2- or Ccr-2-deficient mice. Nat Med 9:1390–1397

    Article  CAS  PubMed  Google Scholar 

  4. Penfold PL, Provis JM, Billson FA (1987) Age-related macular degeneration: ultrastructural studies of the relationship of leucocytes to angiogenesis. Graefes Arch Clin Exp Ophthalmol 225:70–76

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  6. Mo FM, Proia AD, Johnson WH, Cyr D, Lashkari K (2010) Interferon gamma-inducible protein-10 (IP-10) and eotaxin as biomarkers in age-related macular degeneration. Invest Ophthalmol Vis Sci 51:4226–4236

    Article  PubMed  Google Scholar 

  7. Chau KY, Sivaprasad S, Patel N, Donaldson TA, Luthert PJ, Chong NV (2008) Plasma levels of matrix metalloproteinase-2 and -9 (MMP-2 and MMP-9) in age-related macular degeneration. Eye (Lond) 22:855–859

    Article  CAS  Google Scholar 

  8. Sivaprasad S, Adewoyin T, Bailey TA, Dandekar SS, Jenkins S, Webster AR, Chong NV (2007) Estimation of systemic complement C3 activity in age-related macular degeneration. Arch Ophthalmol 125:515–519

    Article  CAS  PubMed  Google Scholar 

  9. Reynolds R, Rosner B, Seddon JM (2010) Serum lipid biomarkers and hepatic lipase gene associations with age-related macular degeneration. Ophthalmology 117:1989–1995

    Article  PubMed Central  PubMed  Google Scholar 

  10. Klein R, Myers CE, Cruickshanks KJ, Gangnon RE, Danforth LG, Sivakumaran TA, Iyengar SK, Tsai MY, Klein BEK (2014) Markers of inflammation, oxidative stress, and endothelial dysfunction and the 20-year cumulative incidence of early age-related macular degeneration: the Beaver Dam Eye Study. JAMA Ophthalmol 132:446–455

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Wu KHC, Tan AG, Rochtchina E, Favaloro EJ, Williams A, Mitchell P, Wang JJ (2007) Circulating inflammatory markers and hemostatic factors in age-related maculopathy: a population-based case-control study. Invest Ophthalmol Vis Sci 48:1983–1988

    Article  PubMed  Google Scholar 

  12. Cha DM, Woo SJ, Kim H-J, Lee C, Park KH (2013) Comparative analysis of aqueous humor cytokine levels between patients with exudative age-related macular degeneration and normal controls. Invest Ophthalmol Vis Sci 54:7038–7044

    Article  CAS  PubMed  Google Scholar 

  13. Martin DF, Maguire MG, Ying G, Grunwald JE, Fine SL, Jaffe GJ (2011) Ranibizumab and bevacizumab for neovascular age-related macular degeneration. N Engl J Med 364:1897–1908

    Article  CAS  PubMed  Google Scholar 

  14. Gasperini JL, Fawzi AA, Khondkaryan A, Lam L, Chong LP, Eliott D, Walsh AC, Hwang J, Sadda SR (2012) Bevacizumab and ranibizumab tachyphylaxis in the treatment of choroidal neovascularisation. Br J Ophthalmol 96:14–20

    Article  PubMed  Google Scholar 

  15. Schaal S, Kaplan HJ, Tezel TH (2008) Is there tachyphylaxis to intravitreal anti-vascular endothelial growth factor pharmacotherapy in age-related macular degeneration? Ophthalmology 115:2199–2205

    Article  PubMed  Google Scholar 

  16. Zimmermann J, Krauthausen M, Hofer MJ, Heneka MT, Campbell IL, Müller M (2013) CNS-targeted production of IL-17A induces glial activation, microvascular pathology and enhances the neuroinflammatory response to systemic endotoxemia. PLoS One 8:e57307

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Toussirot E (2012) The IL23/Th17 pathway as a therapeutic target in chronic inflammatory diseases. Inflamm. Allergy Drug Targets 11:159–168

    Article  CAS  Google Scholar 

  18. Siakavellas SI, Bamias G (2012) Role of the IL-23/IL-17 Axis in Crohn’s Disease. Discov Med 14:253–262

    PubMed  Google Scholar 

  19. Dinarello CA (2009) Immunological and inflammatory functions of the interleukin-1 family. Annu Rev Immunol 27:519–550

    Article  CAS  PubMed  Google Scholar 

  20. Jovanovic DV, Di Battista JA, Martel-Pelletier J, Jolicoeur FC, He Y, Zhang M, Mineau F, Pelletier JP (1998) IL-17 stimulates the production and expression of proinflammatory cytokines, IL-beta and TNF-alpha, by human macrophages. J Immunol 160:3513–3521

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Mrs. Christine Oeruen for her technical assistance. We thank Dr. Reinhard Vonthein, Luebeck University, Institute for Medical Biometry and Statistics (IMBS), Centre for Clinical Trials for his valuable advice during statistical evaluation. The work was supported by Novartis Pharma GmbH, Nürnberg, Germany.

Conflict of interest

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Khaled Nassar.

Additional information

Khaled Nassar and Salvatore Grisanti should be considered as equivalent first authors

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nassar, K., Grisanti, S., Elfar, E. et al. Serum cytokines as biomarkers for age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 253, 699–704 (2015). https://doi.org/10.1007/s00417-014-2738-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00417-014-2738-8

Keywords

Navigation