Osteopontin and Other Regulators of Angiogenesis and Fibrogenesis in the Vitreous from Patients with Proliferative Vitreoretinal Disorders

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

doi:10.1155/2012/493043

Abstract

The aim of this study was to determine the levels of the angiogenic and fibrogenic factors osteopontin (OPN), high-mobility group box-1 (HMGB1), and connective tissue growth factor (CTGF) and the antiangiogenic and antifibrogenic pigment epithelium-derived factor (PEDF) in the vitreous fluid from patients with proliferative diabetic retinopathy (PDR), proliferative vitreoretinopathy (PVR), and rhegmatogenous retinal detachment with no PVR (RD). Vitreous samples from 48 PDR, 17 PVR and 30 RD patients were studied by enzyme-linked immunosorbent assay. OPN, HMGB1, CTGF, and PEDF levels were significantly higher in PDR patients than in RD patients (P < 0.001; 0.002; <0.001; <0.001, resp.). CTGF and PEDF levels were significantly higher in PVR patients than in RD patients (P < 0.001; 0.004, resp.). Exploratory logistic regression analysis identified significant associations between PDR and high levels of HMGB1, CTGF and PEDF, between PDR with active neovascularization and high levels of CTGF and PEDF, and between PDR with traction retinal detachment and high levels of HMGB1. In patients with PDR, there were significant correlations between the levels of PEDF and the levels of OPN (r = 0.544, P = 0.001), HMGB1 (r = 0.719, P < 0.001), and CTGF (r = 0.715, P < 0.001). In patients with PVR, there were significant correlations between the levels of OPN and the levels of HMGB1 (r = 0.484, P = 0.049) and PEDF (r = 0.559, P = 0.02). Our findings suggest that OPN, HMGB1, and CTGF contribute to the pathogenesis of proliferative vitreoretinal disorders and that increased levels of PEDF may be a response to counterbalance the activity of angiogenic and fibrogenic factors in PDR and PVR.

Highlights

Ischemia-induced pathologic growth of new blood vessels and expansion of extracellular matrix (ECM) in association with the outgrowth of fibrovascular epiretinal membranes at the vitreoretinal interface is the pathological hallmark in proliferative diabetic retinopathy (PDR) and often leads to catastrophic loss of vision due to vitreous hemorrhage and/or traction retinal detachment
We examined the levels of the angiogenic and fibrogenic factors OPN, high-mobility group box-1 (HMGB1), and connective tissue growth factor (CTGF) and the antiangiogenic and antifibrogenic pigment epithelium-derived factor (PEDF) in the vitreous fluid from patients with PDR, proliferative vitreoretinopathy (PVR), and RD and their relationship with PDR clinical disease activity
We found upregulation of OPN, HMGB1, CTGF, and PEDF in the vitreous from PDR patients with active neovascularization compared with patients with quiescent PDR, PVR, and RD

Summary

Introduction

Ischemia-induced pathologic growth of new blood vessels and expansion of extracellular matrix (ECM) in association with the outgrowth of fibrovascular epiretinal membranes at the vitreoretinal interface is the pathological hallmark in proliferative diabetic retinopathy (PDR) and often leads to catastrophic loss of vision due to vitreous hemorrhage and/or traction retinal detachment. The key cellular mediator of fibrosis is the myofibroblast, a cell type differentiated from quiescent fibroblasts. These are contractile cells, characterized by the expression of α-smooth muscle actin (αSMA), and their presence is a marker of progressive disease. They have the capacity to produce several ECM components including collagen resulting in fibrosis [2]. A number of proinflammatory, proangiogenic, profibrogenic, and immunomodulating factors may be linked to the development and progression of proliferative vitreoretinal disorders, such as osteopontin (OPN), high-mobility group box-1 (HMGB1), connective tissue growth factor (CTGF), and pigment epithelium-derived factor (PEDF)

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