Abstract

PurposeProliferative Diabetic Retinopathy (PDR) and Eales' Disease (ED) have different aetiologies although they share certain common clinical symptoms including pre-retinal neovascularization. Since there is a need to understand if the shared end-stage angiogenic pathology of PDR and ED is driven by common stimulating factors, we have studied the cytokines contained in vitreous from both patient groups and analyzed the angiogenic potential of these samples in vitro.Material and MethodsVitreous samples from patients with PDR (n = 13) and ED (n = 5) were quantified for various cytokines using a cytokine biochip array and sandwich ELISA. An additional group of patients (n = 5) with macular hole (MH) was also studied for comparison. To determine the angiogenic potential of these vitreous samples, they were analyzed for their ability to induce tubulogenesis in human microvascular endothelial cells. Further, the effect of anti-VEGF (Ranibizumab) and anti-IL-6 antibodies were studied on vitreous-mediated vascular tube formation.ResultsElevated levels of IL-6, IL-8, MCP-1 and VEGF were observed in vitreous of both PDR and ED when compared to MH. PDR and ED vitreous induced greater levels of endothelial cell tube formation compared to controls without vitreous (P<0.05). When VEGF in vitreous was neutralized by clinically-relevant concentrations of Ranibizumab, tube length was reduced significantly in 5 of 6 PDR and 3 of 5 ED samples. Moreover, when treated with IL-6 neutralizing antibody, apparent reduction (71.4%) was observed in PDR vitreous samples.ConclusionsWe have demonstrated that vitreous specimens from PDR and ED patients share common elevations of pro-inflammatory and pro-angiogenic cytokines. This suggests that common cytokine profiles link these two conditions.

Highlights

  • Proliferative Diabetic Retinopathy (PDR) and Eales’ Disease (ED) are potentially blinding vitreoretinal diseases

  • Elevated levels of IL-6, IL-8, monocyte chemoattractant protein-1 (MCP-1) and vascular endothelial growth factor (VEGF) were observed in vitreous of both PDR and ED when compared to macular hole (MH)

  • PDR and ED vitreous induced greater levels of endothelial cell tube formation compared to controls without vitreous (P, 0.05)

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Summary

Introduction

Proliferative Diabetic Retinopathy (PDR) and Eales’ Disease (ED) are potentially blinding vitreoretinal diseases. ED is an idiopathic inflammatory venous occlusion that primarily affects the peripheral retina of healthy young men (20–30 years). Retinal changes in ED include periphlebitis, peripheral nonperfusion and neovascularization. Visual loss is characteristically caused by bilateral recurrent vitreous hemorrhage [1], [2]. PDR and ED have different etiology, the symptoms and signs of these diseases run parallel to each other with some differences [3]. We have previously observed this commonality in the presence of inflammatory cytokines [interleukin-6 (IL-6), interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1)] and vascular endothelial growth factor (VEGF) in vitreous [4]

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