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

Abstract

Purpose 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. Methods 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). Results 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. Conclusions 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.

A review of the multifunctionality of angiopoietin-like 4 in eye disease

“…The severity and socio-economic effect of AMD combined with its increasing occurrence requires immediate attention [ 122 ]. Ioanna et al [ 123 ] found elevated plasma levels of ANGPTL4 in dry AMD patients suggesting new therapeutic target for dry AMD, a finding consistent with the conclusions of the study of Park and co-workers [ 124 ] which investigated the relationship between aqueous ANGPTL4 levels and clinical features in neovascular AMD, and found that ANGPTL4 level was related to the lesion area and the frequency of anti-VEGF treatment. Both studies suggested that ANGPTL4 may be a possible diagnostic and therapeutic biomarker in AMD.…”

Associations of MicroRNAs, Angiogenesis-Regulating Factors and CFH Y402H Polymorphism—An Attempt to Search for Systemic Biomarkers in Age-Related Macular Degeneration

“…Our results correspond with the ongoing research on the role of PlGF and FGF-basic in coordination with VEGF in CNV progression. However, our finding on PlGF downregulation stands in contrary to recent results by Ioanna et al who have shown elevated plasma levels of PlGF in wet AMD [54]. On the other hand, Zhou et al have recently suggested [55], based on their study on neovascular glaucoma, local PlGF and VEGF production directly in the eye as opposed to transudation of these factors from blood into the vitreous.…”

Toll-Like Receptor Signalling Pathways Regulate Hypoxic Stress Induced Fibroblast Growth Factor but Not Vascular Endothelial Growth Factor-A in Human Microvascular Endothelial Cells

“…Hypoxia is a condition in which oxygen tension is adequately deficient at tissue level, this then upregulates cellular expression of hypoxia-inducible factor-1α (HIF1-α) [3]. HIF1α regulates the synthesis and release of angiogenic factors such as fibroblast growth factor (FGF-2) and VEGF-A [4]. Hypoxia-activated endothelin-1/endothelin receptor signalling has been implicated in VEGF-A production from macrovascular endothelial cells and melanoma cells [5].…”