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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. doi: https://doi.org/.
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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.
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.
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.
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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