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Jutamas Suwanpradid, Zhimin Xu, Subhadra P. Narayanan, William R. Caldwell, Ruth B. Caldwell; Arginase 2 Mediates Vascular Injury through Peroxynitrite Formation in a Mouse Model of Oxygen-induced Retinopathy. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3977.
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© ARVO (1962-2015); The Authors (2016-present)
Inhibition of arginase (A) has been suggested to have therapeutic value in the management of cardiovascular diseases. Moreover, our previous studies showed that A2 knockout (ko) alone or in combination with heterozygous ko of A1 reduces vascular injury in a mouse model of oxygen-induced retinopathy (ARVO, 2010). Now, we have further characterized this protective effect and examined the role of peroxidative stress in the pathological process.
Mice (A2ko, A1ko, WT) were placed in 70% oxygen from p7-p12and returned to room air for various times. The hyperoxia exposure causes obliteration of the developing vessels which leads to a condition of relative ischemia that is characterized by elevated oxidative stress and pathological vitreo-retinal neovascularization when the mice are returned to normal oxygen atmosphere. Mice were sacrificed at different times and their retinas were processed to determine the effects of arginase deletion on vaso-obliteration and peroxynitrite formation following the hyperoxia treatment.
Measurement of the central avascular zone showed that on p8 the area of vaso-obliteration in the retinas of A2ko mice was equivalent to that in the WT mice (29% vs 32%). However, on p9 the avascular zone in the A2 knockout retina was significantly smaller than that in the WT (25% vs 33%, P<0.05) suggesting that vascular repair had already begun. This recovery continued with time and at p17 the avascular area in the A2 ko was further reduced as compared with the WT (5% vs 11%, P<0.05). By contrast vascular repair was not improved in the A1ko retina. On p17 the avascular area in the A1ko retina was 21% vs 12% in the WT controls. The accelerated vascular repair in the A2ko retina was associated with a 1.6 fold decrease in peroxynitrite formation as compared with the WT mice (P<0.05).
Arginase 2 plays a key role in retinal vascular injury and repair during oxygen induced retinopathy through a mechanism involving peroxynitrite formation. Arginase 1 is not involved in this process.
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