Angiogenic and Vasculogenic Factors in the Vitreous from Patients with Proliferative Diabetic Retinopathy

Ahmed M Abu El-Asrar,Karel Geboes,Dustan Kangave,Mohd Imtiaz Nawaz,Mohammed Mairaj Siddiquei

doi:10.1155/2013/539658

Abstract

This study was conducted to determine levels of angiogenic and endothelial progenitor cell mobilizing (vasculogenic) factors in vitreous fluid from proliferative diabetic retinopathy (PDR) patients and correlate their levels with clinical disease activity. Vascular endothelial growth factor (VEGF), soluble vascular endothelial growth factor receptor-2 (sVEGFR-2), stem cell factor (SCF), soluble c-kit (s-kit), endothelial nitric oxide synthase (eNOS), and prostaglandin E2 (PGE2) levels were measured by ELISA in vitreous samples from 34 PDR and 15 nondiabetic patients. eNOS was not detected. VEGF, sVEGFR-2, SCF, and s-kit levels were significantly higher in PDR with active neovascularization compared with quiescent PDR and nondiabetic patients (P < 0.001; 0.007; 0.001; <0.001, resp.). In contrast, PGE2 levels were significantly higher in nondiabetic patients compared with PDR patients (P < 0.001). There were significant correlations between levels of sVEGFR-2 versus SCF (r = 0.950, P < 0.001), sVEGFR-2 versus s-kit (r = 0.941, P < 0.001), and SCF versus s-kit (r = 0.970, P < 0.001). Our findings suggest that upregulation of VEGF, sVEGFR-2, SCF, and s-kit supports the contributions of angiogenesis and vasculogenesis in pathogenesis of PDR.

Highlights

Angiogenesis, the process by which new vascular networks develop from preexisting vessels, is a hallmark feature of proliferative diabetic retinopathy (PDR)
We demonstrated that bone marrow-derived CD133+ endothelial progenitor cells (EPCs) and c-kit+ cells contribute to the new vessel formation in PDR fibrovascular epiretinal membranes [3, 4]
The present study is to our knowledge the first to assess the levels of sVEGFR-2, stem cell factor (SCF), and s-kit in the vitreous fluid from patients with PDR

Summary

Introduction

Angiogenesis, the process by which new vascular networks develop from preexisting vessels, is a hallmark feature of proliferative diabetic retinopathy (PDR). Increasing evidence suggests that vasculogenesis, the de novo formation of blood vessels from circulating bone marrow-derived endothelial progenitor cells (EPCs), can contribute to neovascularization. Recent studies have shown that circulating bone marrow-derived EPCs home to the ischemic region, differentiate into mature endothelial cells in situ, and can contribute to the process of neovascularization [1, 2]. VEGF binds with high affinity and activates two tyrosine kinase receptors, VEGFR-1 (Flt-1) and VEGFR-2 (KDR in humans/Flk-1 in mice). These receptors regulate physiological as well as pathological angiogenesis. VEGFR-2 has strong tyrosine kinase activity and is the major positive signal transducer for pathological angiogenesis including cancer and diabetic retinopathy as well as microvascular permeability [7]. It is unknown whether the sVEGFR-2 is a product of ectodomain shedding from cell-surface VEGFR-2 or a product of alternative mRNA splice variation [8, 9]

Methods

Results

Conclusion