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Z. Wu, S. Wang, C.M. Sorenson, N. Sheibani; Hypoxia-Mediated Loss of Astrocytes Promotes the Pathogenesis of Oxygen-Induced Ischemic Retinopathy . Invest. Ophthalmol. Vis. Sci. 2003;44(13):2095.
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Purpose: Astrocytes play an integral role in the development and normal function of retinal vasculature. This report investigates whether the presence of NG2 positive pericytes prevents hyperoxia-induced retinal vessel obliteration in a murine model of oxygen-induced ischemic retinopathy and what role astrocytes play in this process. Methods: Retinas from mice of different age (P0 to P21), as well as those exposed to 75% oxygen for 1 day or 5 days and then recovered in room air for 1 day or 5 days, were stained with antibodies to PECAM-1, NG2, alpha-SMA, and GFAP. The endothelial cell/pericyte ratios were determined using trypsin-digests of retina preparation from P7 and P21 mice. Results: During normal development, the characteristic honeycomb pattern of vessel formation was observed in the superficial layer. This is accomplished by proliferation and migration of endothelial cells over a preexisting astrocytes template. The NG2 positive pericytes were found to be present from birth throughout the vascular plexus including in the newly formed vessels. However, differentiating alpha-SMA-positive SMCs were only present just on the large radial vessels. There were no differences in the endothelial cell/pericytes ratio between P7 and P21 mice. During the hyperoxia phase astrocytes remained intact, while endothelial cells of the central capillary vessels were lost. This was followed by a decrease in the number of NG2-positive pericytes. However, hypoxia resulted in a rapid loss of retinal astrocytes. This may contribute to the abnormal morphology adapted by new vasculature and expression of alpha-SMA by NG2-positive pericytes in the intra-retinal and pre-retinal vasculature. Conclusion: During normal development and at various stages of oxygen-induced ischemic retinopathy, neither the pericyte ensheathment of vessels, nor the changes in endothelial cell/pericyte ratios prevent normal and pathological angiogenesis. We believe that it is the sensitivity of the endothelial cells to oxygen levels that modulates retinal vascular development and ischemia-driven neovascularization, which is intimately influenced by the survival and appropriate functioning of the astrocytes.
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