Skip to main content
Erschienen in: Graefe's Archive for Clinical and Experimental Ophthalmology 5/2015

01.05.2015 | Retinal Disorders

Serum cytokines as biomarkers for age-related macular degeneration

verfasst von: Khaled Nassar, Salvatore Grisanti, Elshaymaa Elfar, Julia Lüke, Matthias Lüke, Swaantje Grisanti

Erschienen in: Graefe's Archive for Clinical and Experimental Ophthalmology | Ausgabe 5/2015

Einloggen, um Zugang zu erhalten

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.
Literatur
1.
Zurück zum Zitat 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–S14CrossRefPubMed 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–S14CrossRefPubMed
2.
Zurück zum Zitat 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 115:116–126CrossRefPubMed 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 115:116–126CrossRefPubMed
3.
Zurück zum Zitat 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 9:1390–1397CrossRefPubMed 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 9:1390–1397CrossRefPubMed
4.
Zurück zum Zitat 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 225:70–76CrossRefPubMed 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 225:70–76CrossRefPubMed
5.
Zurück zum Zitat Edwards AO, Ritter R, Abel KJ, Manning A, Panhuysen C, Farrer LA (2005) Complement factor H polymorphism and age-related macular degeneration. Science 308:421–424CrossRefPubMed Edwards AO, Ritter R, Abel KJ, Manning A, Panhuysen C, Farrer LA (2005) Complement factor H polymorphism and age-related macular degeneration. Science 308:421–424CrossRefPubMed
6.
Zurück zum Zitat 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 51:4226–4236CrossRefPubMed 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 51:4226–4236CrossRefPubMed
7.
Zurück zum Zitat 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) 22:855–859CrossRef 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) 22:855–859CrossRef
8.
Zurück zum Zitat 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 125:515–519CrossRefPubMed 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 125:515–519CrossRefPubMed
9.
Zurück zum Zitat Reynolds R, Rosner B, Seddon JM (2010) Serum lipid biomarkers and hepatic lipase gene associations with age-related macular degeneration. Ophthalmology 117:1989–1995CrossRefPubMedCentralPubMed Reynolds R, Rosner B, Seddon JM (2010) Serum lipid biomarkers and hepatic lipase gene associations with age-related macular degeneration. Ophthalmology 117:1989–1995CrossRefPubMedCentralPubMed
10.
Zurück zum Zitat 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 132:446–455CrossRefPubMedCentralPubMed 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 132:446–455CrossRefPubMedCentralPubMed
11.
Zurück zum Zitat 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 48:1983–1988CrossRefPubMed 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 48:1983–1988CrossRefPubMed
12.
Zurück zum Zitat 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 54:7038–7044CrossRefPubMed 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 54:7038–7044CrossRefPubMed
13.
Zurück zum Zitat 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 364:1897–1908CrossRefPubMed 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 364:1897–1908CrossRefPubMed
14.
Zurück zum Zitat 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 96:14–20CrossRefPubMed 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 96:14–20CrossRefPubMed
15.
Zurück zum Zitat Schaal S, Kaplan HJ, Tezel TH (2008) Is there tachyphylaxis to intravitreal anti-vascular endothelial growth factor pharmacotherapy in age-related macular degeneration? Ophthalmology 115:2199–2205CrossRefPubMed Schaal S, Kaplan HJ, Tezel TH (2008) Is there tachyphylaxis to intravitreal anti-vascular endothelial growth factor pharmacotherapy in age-related macular degeneration? Ophthalmology 115:2199–2205CrossRefPubMed
16.
Zurück zum Zitat 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:e57307CrossRefPubMedCentralPubMed 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:e57307CrossRefPubMedCentralPubMed
17.
Zurück zum Zitat Toussirot E (2012) The IL23/Th17 pathway as a therapeutic target in chronic inflammatory diseases. Inflamm. Allergy Drug Targets 11:159–168CrossRef Toussirot E (2012) The IL23/Th17 pathway as a therapeutic target in chronic inflammatory diseases. Inflamm. Allergy Drug Targets 11:159–168CrossRef
18.
Zurück zum Zitat Siakavellas SI, Bamias G (2012) Role of the IL-23/IL-17 Axis in Crohn’s Disease. Discov Med 14:253–262PubMed Siakavellas SI, Bamias G (2012) Role of the IL-23/IL-17 Axis in Crohn’s Disease. Discov Med 14:253–262PubMed
19.
Zurück zum Zitat Dinarello CA (2009) Immunological and inflammatory functions of the interleukin-1 family. Annu Rev Immunol 27:519–550CrossRefPubMed Dinarello CA (2009) Immunological and inflammatory functions of the interleukin-1 family. Annu Rev Immunol 27:519–550CrossRefPubMed
20.
Zurück zum Zitat 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 160:3513–3521PubMed 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 160:3513–3521PubMed
Metadaten
Titel
Serum cytokines as biomarkers for age-related macular degeneration
verfasst von
Khaled Nassar
Salvatore Grisanti
Elshaymaa Elfar
Julia Lüke
Matthias Lüke
Swaantje Grisanti
Publikationsdatum
01.05.2015
Verlag
Springer Berlin Heidelberg
Erschienen in
Graefe's Archive for Clinical and Experimental Ophthalmology / Ausgabe 5/2015
Print ISSN: 0721-832X
Elektronische ISSN: 1435-702X
DOI
https://doi.org/10.1007/s00417-014-2738-8

Weitere Artikel der Ausgabe 5/2015

Graefe's Archive for Clinical and Experimental Ophthalmology 5/2015 Zur Ausgabe

Neu im Fachgebiet Augenheilkunde

Metastase in der periokulären Region

Metastasen Leitthema

Orbitale und periokuläre metastatische Tumoren galten früher als sehr selten. Aber mit der ständigen Aktualisierung von Medikamenten und Nachweismethoden für die Krebsbehandlung werden neue Chemotherapien und Strahlenbehandlungen eingesetzt. Die …

Staging und Systemtherapie bei okulären und periokulären Metastasen

Metastasen Leitthema

Metastasen bösartiger Erkrankungen sind die häufigsten Tumoren, die im Auge diagnostiziert werden. Sie treten bei ungefähr 5–10 % der Patienten mit soliden Tumoren im Verlauf der Erkrankung auf. Besonders häufig sind diese beim Mammakarzinom und …

CME: Wundheilung nach Trabekulektomie

Trabekulektomie CME-Artikel

Wird ein Glaukom chirurgisch behandelt, ist die anschließende Wundheilung von entscheidender Bedeutung. In diesem CME-Kurs lernen Sie, welche Pathomechanismen der Vernarbung zugrunde liegen, wie perioperativ therapiert und Operationsversagen frühzeitig erkannt werden kann.

„standard operating procedures“ (SOP) – Vorschlag zum therapeutischen Management bei periokulären sowie intraokulären Metastasen

Metastasen Leitthema

Peri- sowie intraokuläre Metastasen sind insgesamt gesehen selten und meist Zeichen einer fortgeschrittenen primären Tumorerkrankung. Die Therapie ist daher zumeist palliativ und selten kurativ. Zudem ist die Therapiefindung sehr individuell. Die …

Update Augenheilkunde

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.