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D. G. Morrison, X. Shang, J. Penn; Differential Role of IGF in VEGF Induction in Astrocytes and Müller Cells. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2628.
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Retinopathy of prematurity (ROP) is a potentially blinding disease of the eye caused by neovascularization of the retina. Serum insulin-like growth factor (IGF) is placentally produced and is low in preterm infants. Clinically, low IGF levels at birth correlate to an increased risk of ROP.1 IGF is known to stimulate vascular endothelial growth factor (VEGF) production in cultured astrocytes. Muller cells in culture do not respond to IGF stimulation, but produce significantly greater amounts of VEGF than other cell types.2 The purpose of this study is to evaluate the IGF-1 signaling system in primary Muller cells and astrocytes.
Primary cultures of retinal Müller cells and brain astrocytes were isolated from P7 and P1 newborn rats, respectively. Cultures were incubated in normoxia (21% O2) and hypoxia (~0%O2) for 24 hours. IGF-1 secretion was then measured by ELISA. Cells were lysed and the protein level was used to standardize results for cell density within each plate. Western blot analysis was performed on cell lysates to determine the presence of the IGF-1 receptor in each cell type.
Müller cells lack significant IGF-1 receptor and do not produce significant IGF-1. Astrocytes demonstrate the clear presence of IGF-1 receptor and produce IGF-1 constitutively in nomoxia and hypoxia.
Müller cells lack the cellular machinery to produce or respond to IGF-1. IGF-1 is significantly involved in astrocyte VEGF production. This study lends additional support to the notion that astrocytes may have a larger role in IGF-dependent vasculogenesis than Müller cells. Clinically, IGF replacement may aid in vasculogenesis without increasing Müller cell-dependent, and thus pathologic, VEGF production.
1. Hellstrom A, et al. Low IGF-I suppresses VEGF-survival signaling in retinal endothelial cells: direct correlation with clinical retinopathy of prematurity. Proc Natl Acad Sci USA . 2001; 98(10):5804-8.
2. Morrison D, Aschner M, Penn J. Vascular endothelial growth factor response to insulin-like growth factor in normoxic and hypoxic cell culture. Ophthalmol. Vis. Sci. 2007 48: E-Abstract 1735.
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