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JD Ash, A Palomar, D Charles, M Balkis; Oxygen-Induced Inhibition of Vascular Endothelial Cell and Retinal Astrocyte Development is Age-Dependent in Mice . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1284.
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Purpose: In humans, the youngest premature infants have the greatest risk for developing retinopathy of prematurity. This suggest there are age-dependent effects of oxygen exposure. Retinal astrocytes and vascular endothelial cells have essential roles in the growth and maintenance of the retinal vasculature. The growth and development of both cell types has previously been shown to be affected by high oxygen. In this study we sought to determine if developmental age is an important factor in determining the response of either cell type to high oxygen. Methods: Mice were exposed to 75% oxygen in three age groups. 1) from embryonic day 15 to postnatal day 9 (E15-P9). 2) from P2 to P9. 3) from P7 to P13. Following exposure, retinas were collected and stained for vascular endothelial cells (gs lectin), and for astrocytes (S100, or GFAP-GFP transgenic mice). Retinas were then flatmounted and analyzed by fluorescent microscopy. Results: Mice exposed from E15 to P9 completely lacked vascular endothelial cells in the retina. The vasculature in P7-P13 exposed mice consisted of the superficial layer but with significant capillary loss in the central retina as described previously. The retinas from P2-P9 exposed mice had an intermediate phenotype with most retinas containing only islands of endothelial cell patches that were not connected by arteries or veins. Oxygen exposure reduced the number of GFAP-expressing astrocytes. The youngest exposed mice had the fewest GFAP-positive astrocytes. Interestingly, oxygen exposure did not affect the migration of astrocyte precursors. In areas of the younger exposed retinas where endothelial cells failed to populate, the astrocytes failed to mature. Conclusion: The growth of the retinal vasculature was inhibited by oxygen exposure in an age dependent manner, with the youngest exposure age resulting in a complete block in retinal vascular development. The inhibition of vascular growth correlated with inhibited differentiation of retinal astrocytes. The data suggest that the physical and molecular interaction between endothelial cells and astrocytes is important for the maturation of astrocytes.
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