September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Levels of vitreous angiopoietin-2 are associated with vitreous levels of inflammatory cytokines in patients with age-related macular degeneration or diabetic retinopathy
Author Affiliations & Notes
  • Everson Nogoceke
    Ophthalmology Discovery & Biomarkers, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Basel, Switzerland
  • Gonzalo Durán-Pacheco
    Pharma Research and Early Development, Pharmaceutical Sciences , Roche Innovation Center Basel, F. Hoffmann - La Roche Ltd., Basel, Switzerland
  • Gabriella Widmer
    Ophthalmology Discovery & Biomarkers, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Basel, Switzerland
  • Paolo Piraino
    Pvalue Research SRL, Piacenza, Italy
  • Michael Koss
    Department of Ophthalmology, University of Heidelberg, Heidelberg, Germany
  • Guido Hartmann
    Ophthalmology Discovery & Biomarkers, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Basel, Switzerland
  • Footnotes
    Commercial Relationships   Everson Nogoceke, F. Hoffmann-La Roche Ltd (E); Gonzalo Durán-Pacheco, F. Hoffmann-La Roche Ltd (E); Gabriella Widmer, F. Hoffmann-La Roche Ltd (E); Paolo Piraino, F. Hoffmann-La Roche Ltd (C); Michael Koss, F. Hoffmann-La Roche Ltd (C); Guido Hartmann, F. Hoffmann-La Roche Ltd (E)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 4813. doi:
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      Everson Nogoceke, Gonzalo Durán-Pacheco, Gabriella Widmer, Paolo Piraino, Michael Koss, Guido Hartmann; Levels of vitreous angiopoietin-2 are associated with vitreous levels of inflammatory cytokines in patients with age-related macular degeneration or diabetic retinopathy. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4813.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Increased levels of inflammatory cytokines have been reported in vitreous of patient with neovascular retinal diseases including age-related macular degeneration (AMD) and diabetic retinopathy (DR). However, the role of cytokines in the pathophysiology of these diseases remains unclear. We investigated whether the concentration of angiopoietin-2 (Ang-2), a potent pro-angiogenic factor and promising target for new treatments in neovascular diseases, is associated with levels of inflammatory cytokines in vitreous of patients with AMD and DR.

Methods : We performed a retrospective cross-sectional analysis of vitreous samples of patients with AMD (N=119) and DR (N=41) using multiplex Luminex assays to measure the concentration of Ang-2 and interleukins IL-6, IL-7, and IL-8. Undiluted vitreous samples were collected by 23-gauge core vitrectomy prior to drug application (1). Data was analyzed by descriptive statistics and Spearman's rho rank correlation computed after pair wise deletion of missing values.

Results : The median vitreous Ang-2 concentration was 139 pg/mL (IQR=225.8) in AMD patients and 302.5 pg/mL (IQR=460.0) in DR patients. Median vitreous concentrations of IL-6, IL-7 and IL-8 were respectively 5.3 pg/mL (IQR=17.7), 13.4 pg/mL (IQR=15.1) and 3.1 pg/mL (IQR=5.3) in AMD, and 15.2 pg/mL (IQR=34.3), 19.8 pg/mL (IQR=19.4) and 11.6 pg/mL (IQR=13.9) in DR patients. Levels of Ang-2 were associated with vitreous concentrations of IL-6 (Rho=0.26, p=0.0041), IL-7 (Rho=0.57, p<0.001) and IL-8 (Rho=0.22, p=0.019) in AMD patients, and with IL-6 (Rho=0.46, p=0.0024), IL-7 (Rho=0.52, p<0.001) and IL-8 (Rho=0.66, p<0.001) in DR patients. Vitreous levels of Ang-2 were also associated with age of AMD patients (Rho=0.4, p<0.001) but not with age of DR subjects (Rho = -0.06, p = 0.701). Similarly, age was also associated with vitreous concentration of IL-6 (Rho=0.33, p<0.001), IL-7 (Rho=0.3, p<0.001) and IL-8 (Rho=0.24, p=0.0105) only in AMD.

Conclusions : Vitreous levels of Ang-2 are associated with vitreous levels of inflammatory cytokines in AMD and DR. Age, a major risk factor of AMD, is associated with rising vitreous levels of both Ang-2 and inflammatory cytokines. The results suggest that inflammation, which is increased with aging or diabetes, may be linked to angiogenesis in AMD and DR through increased concentration of Ang-2.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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