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Graefes Arch Clin Exp Ophthalmol. 2018 Feb;256(2):325-332. doi: 10.1007/s00417-017-3846-z. Epub 2017 Nov 25.

Plasma levels of hypoxia-regulated factors in patients with age-related macular degeneration.

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Department of Ophthalmology, University Hospital Zurich, Frauenklinikstrasse 24, 8091, Zurich, Switzerland.
Lab for Retinal Cell Biology, Department of Ophthalmology, Zurich Centre for Integrative Human Physiology (ZIHP), and Neuroscience Centre (ZNZ), University of Zurich, Zurich, Switzerland.
Department of Ophthalmology, University Hospital Zurich, Frauenklinikstrasse 24, 8091, Zurich, Switzerland.



Various hypoxia-related proteins are differentially expressed in the retina and secreted to the vitreous and/or aqueous humor of patients affected by dry or neovascular age-related macular degeneration (nAMD). To determine whether these conditions alter concentrations of cytokines also in the systemic circulation, we measured plasma levels of six hypoxia-related proteins.


Plasma was prepared from EDTA blood that was collected from patients affected by dry AMD (n = 5), nAMD (n = 11), proliferative diabetic retinopathy (PDR; n = 9), and patients with an epiretinal membrane (ERM; n = 11). ERM samples served as negative controls, PDR samples as positive controls. Protein concentrations of vascular endothelial growth factor (VEGF), erythropoietin (EPO), angiopoietin-like 4 (ANGPTL4), placental growth factor (PlGF), tumor necrosis factor alpha (TNF-α), and pigment epithelium-derived factor (PEDF) were determined by enzyme-linked immunosorbent assay (ELISA).


The concentration of PlGF was significantly increased in plasma of patients affected by nAMD. Although no statistically significant differences were found for EPO, ANGPTL4, PlGF, TNF-α, and PEDF, the mean concentration of VEGF was lowest in the nAMD group. Plasma concentrations of the six factors did not correlate with gender or age of patients.


nAMD may increase plasma concentrations of PlGF, making it a candidate as a biomarker for the neovascular form of AMD. Other factors, however, were not differentially regulated, suggesting that their systemic concentrations are not generally increased in hypoxia-related retinal diseases.


Age-related macular degeneration; Cytokines; Plasma; Vascular endothelial growth factor

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