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E. L. McFarland, A. Afzal, J. L. Kielczewski, K.-H. Chang, T. Gardiner, M. B. Grant, T. Chan-Ling; IGF Binding Protein-3 (IGFBP3) Affects Endothelial Cell Ensheathment and Apoptosis in Normoxia and in the Oxygen Induced Retinopathy (OIR) Model. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1349.
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The hypoxia regulated factor IGFBP3 has profound effects on the retinal vasculature during development. However, little is known about the cellular mediators and pathways that are responsible for this effect. We asked whether IGFBP3 inhibits hyperoxia-induced apoptosis; what effects it has on endothelial cell ensheathment and whether IGFBP3 modulated inflammation in normoxia and in the OIR model.
On postnatal day 1 (P1), neonatal pups received intra-vitreal injection of IGFBP3-expressing plasmid under the control of a proliferating endothelial-specific promoter. In addition, the effect of IGFBP3 was examined during normal retinal development. Apoptotic death (TUNEL) of astrocytes (S100), endothelial cells (GS Lectin), pericytes (NG2) and microglia (GS Lectin) were determined using quadruple marker immunohistochemistry on retinal wholemounts.
Increased IGFBP3 expression during normal retinal development resulted in: irregular vascular formations and lack of normal arterial/venous pairing observed at the optic nerve; increased density of astrocytic ensheathment of retinal vessels; a slight increase in inflammatory cells and a significantly greater numbers of TUNEL+ cells. Increased IGFBP3 expression during the hyperoxic phase of the OIR model resulted in: protection of the developing vasculature from hyperoxia-induced regression; increased density of astrocytic ensheathment of vessels; a marked increase in inflammatory cells and significantly greater numbers of TUNEL+ cells. Increased IGFBP3 expression during the hypoxic phase of the OIR model resulted in: reduction in pre-retinal neovascularization; increased density of astrocytic ensheathment of vessels; a marked increase in inflammatory cells and significantly greater numbers of TUNEL+ cells.
These findings suggests that while IGFBP3 has been shown to have many beneficial effects in the OIR model, exact titration of the level of expression is required to gain optimal benefit from this molecule.
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