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J. Suwanpradid, L. Yancey, W. Zhang, Z. Xu, S. P. Narayanan, S. Virmani, A. Patel, S. Brooks, R. W. Caldwell, R. B. Caldwell; Arginase Deletion Protects the Developing Retinal Vasculature From Oxyge-Induced Retinopathy. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4480.
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Arginase inhibition has been suggested to have therapeutic value in the management of cardiovascular diseases. The purpose of this study was to determine whether deletion of arginase genes protects the retinal vasculature from injury during oxygen-induced retinopathy (OIR).
Wild type (WT) C57BL/6J mice and mice homozygous for arginase-2 knockout (A2-/-) alone or in combination with heterozygous knockout of arginase-1 (A1+/- A2-/-) were placed in 70% oxygen from p7-p12 followed by normoxia until p17. Mice were sacrificed either at p12 or p17 . Morphometric analysis of Isolectin-B4 labeled on retinal flatmounts was used to quantify areas of vaso-obliteration and extraretinal neovascularization. Arginase mRNA was measured by quantitative PCR (qPCR).
Measurement of the avascular zone at p12 and p17 showed that the area of vaso-obliteration was significantly reduced in both arginase knockout lines as compared with the WT controls (capillary dropout area at p12 was 21 ± 2 % in arginase knockout vs 35% ± 2% in WT, P= 0.0057; and at p17 it was 5 ±0.5% vs. 11%± 1% P< 0.0001, respectively). The area of extraretinal neovascularization was also decreased in the knockout groups. Arginase-1 mRNA expression increased significantly between p12 and p17 in WT OIR as compared with the WT normoxic controls (P< 0.05). Arginase-2 mRNA level was similar in both groups.
Deletion of the arginase-2 gene (A2-/-) alone or in combination with heterozygous knockout of arginase-1 (A1+/- A2-/-) reduces the vascular injury caused by hyperoxia with little effect on the subsequent angiogenic response. Our results suggest that controlling arginase activity may provide a means for reducing retinal vascular damage in oxidative stress conditions.
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