Hyperoxia‐induced Microvascular Injury Involves Arginase 2‐induced Oxidative Stress, Microglia/Macrophage Activation and Constitutive NOS Downregulation

Abstract

We have shown previously that deletion of arginase 2 (A2) enhances vascular repair in a mouse model of oxygen‐induced retinopathy. Now, we have examined the involvement of arginase activity and A2 expression in oxygen‐induced microvascular injury. Neonatal mice were exposed to 70% oxygen for various times and their retinas were processed to determine the effects of the arginase inhibitor 2(S)‐amino‐6‐boronohexanoic acid (ABH) or A2 deletion on oxygen‐induced vascular degeneration in relation to activation of microglia/macrophages, expression of NOS and oxidative stress. Oxygen‐induced degeneration of the developing retinal vasculature was reduced in mice treated with ABH or in A2 knockout mice as compared with the controls (P<0.05). This vasoprotective effect was associated with blockade of microglia/macrophage activation (P<0.05), normalization of eNOS and nNOS expression and decreased oxidative stress (P<0.05) as compared with the controls. These results indicate that A2 plays a key role in hyperoxia‐induced retinal vascular injury through a mechanism involving oxidative stress, decreases in constitutive NOS expression and activation of microglia/macrophage cells.