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K. Uno, I. A. Bhutto, G. A. Lutty, A. Yerrapureddy, S. P. Reddy, M. Yamamoto, T. W. Prow; Role of Nrf2 in Retinal Vascular Development and the Vaso-Obliterative Phase of Oxygen-Induced Retinopathy. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4050.
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In the initial stage of retinopathy of prematurity (ROP), hyperoxia causes retinal blood vessel obliteration. This is thought to occur in part through oxidative stress-induced apoptosis of endothelial cells. This study was designed to determine what role NF-E2-related factor 2 (Nrf2) plays in this process. Nrf2 is a transcription factor of the antioxidant response element that may protect the retina from oxidative stress in hyperoxia.
Nrf2 knockout mice (K/O), Nrf2 wild type control mice (WT), and C57BL/6 mice (C57) were exposed to hyperoxia (75% O2) or normoxia from P7 through P12. Mice were sacrificed at P9 and P12. Retinas were stained with GSA lectin-Cy3 to visualize retinal blood vessels. Hyperoxia exposed retinas were flat mounted and photographed, then avascular areas were analyzed. Additionally, retinas were cryopreserved after lectin-Cy3 staining and sectioned. Secondary capillaries in sections were then hand-counted.
The avascular areas in K/O P9 mice were significantly larger than that in WT P9 (P=0.01). However, there was no significant difference between KO P12 and WT P12. Avascular areas at P12 were significantly smaller than that at P9 in K/O, WT, and C57 (P=0.0011, P=0.009, and P=0.001 respectively). The numbers of secondary capillaries in air-reared K/O mice were significantly decreased, when compared to WT at P9 (P=0.0082). On the other hand, there was no significant difference between air reared K/O and WT mice at P12.
These data suggest that Nrf2 may play a protective role in retinal vascular development and in the early phase of oxygen-induced vaso-obliteration.
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