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A. Sato, N. Katai, H. Shibuki, T. Kikuchi, N. Yoshimura; Characterization of Gene Expression Changes in Oxygen-induced Retinopathy at the Early Stage of Retinal Neovascularization . Invest. Ophthalmol. Vis. Sci. 2003;44(13):561.
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Purpose: To characterize gene expression changes at the early stage of retinal neovascularization in a mouse model of oxygen-induced retinopathy by using a gene microarray system. Methods: C57BL/6J neonatal mice were exposed to 75% oxygen from the postnatal day 7 to 12 and then returned to the room air. Control mice were kept in room air. Fluorescein angiography was used to determine the day on which oxygen induced retinal neovascularization occurs. On day 15, eyes were enucleated from the control mice and mice suffered from oxygen-induced retinopathy. mRNAs purified from the retinas were labeled and hybridized with probes. Microarray analysis was carried out using cRNA probes on Affimetrix MGU74A chips. Immunohistochemical analysis was also performed to know spatial expression patterns of some genes. Results: Fluorescein-dextran angiography showed occurrence of neovascularization at the junction between the perfused and the nonperfused retina on postnatal day 15. By the light microscopic analysis, neovascular tufts were seen to protrude into the vitreous cavity in mice exposed to oxygen. The microarray used in this study contained 12,488 mouse cDNA and expressed sequence tags (ESTs). Of those, 129 cDNA and ESTs showed significant changes (over 2-fold) in expression between hyperoxia and normoxia groups. The up-regulated genes could be classified into some groups such as growth factors, transcription factors, stress induced proteins, cell markers, and extracellular matrix. Some of them were highly expressed at the vascular glomeruli in retinas of mouse exposed to hyperoxia. Also, there were some up-regulated genes that have not been reported to play a role in retinal neovascularization. Conclusions: The data of gene microarray revealed that several genes including vascular endothelial growth factor, insulin-like growth factor and heat-stress related proteins showed expression changes.
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