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X. Shang, W. M. Watkins, J. S. Penn, D. G. Morrison; Igfbp3 Upregulates Vegf Production in Normoxic Retinal Cell Culture. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3123.
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Retinopathy of prematurity is a blinding disease caused by neovascularization of the retina. Vascular endothelial growth factor (VEGF) has been demonstrated to be necessary and sufficient for both vasculogenesis and angiogenesis in the eye. Recent studies have indicated that insulin-like binding protein 3 (IGFBP3) plays a role in modulating vascular development independent of insulin-like growth factor (IGF). However, the influence of IGFBP3 on VEGF is poorly understood. Our study aims to investigate the role of IGFBP3 in VEGF induction in vitro and in the rat model of ROP.
Rat retinal astrocytes and Muller cells were treated with recombinant IGFBP3 in normoxia and hypoxia. VEGF and IGF1 response was assessed by ELISA. Sprague Dawley rat pups were subject to OIR and had intravitreous injections of IGFBP3 on P5, P9, and P12. The rats were sacrificed on P14 and P20. The retinas were isolated and homogenized and VEGF was measured. The effect of the drug on neovascularization was determined by clock hour and vascular area measurements.
Treatment of rat retinal Muller cells and astrocytes with IGFBP3 caused an increase in VEGF and IGF1 production in a dose dependent manner in normoxic cells (p=0.0035 between highest dose treatment and no treatment), but not in hypoxia. OIR animals treated with intravitreous injections of IGFBP3 demonstrate a 30% decrease in retinal VEGF compared to controls at P20, but no dramatic reduction in retinal neovascularization.
Our preliminary data suggests that IGFBP3 plays a direct role in IGF-1-independent VEGF production in vitro. However, this difference does not correlate with decreased ocular angiogenesis in the OIR model. The potential of IGFBP3 as a therapeutic target in retinopathy of prematurity remains an area of interest
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