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M. Istanboli, M. Al–Shabrawey, M.A. Behzadian, T. Franklin, T. Lemtalsi, D.H. Platt, A.B. El–Remessy, R.B. Caldwell, M. Bartoli; Statin Treatment Is Protective for Oxygen–Induced Retinal Microvascular Injury . Invest. Ophthalmol. Vis. Sci. 2005;46(13):466.
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Purpose: The present study is aimed at determining the effect of statin treatment in preventing oxygen–induced retinal vascular injury. Oxygen–induced vascular injury is a major cause of retinopathy and blindness in infants. Recent studies have shown that inhibitors of HMG–CoA reductase (statins) exert remarkable vasoprotective effects independently of their lipid lowering properties. Statins exert their protective effects also on the retinal microvasculature, as has been shown in a number of disease conditions including diabetic retinopathy and age–related macular degeneration. Methods: Experiments were done in the mouse model of oxygen–induced retinopathy (OIR) in which neonatal mice are maintained in 75% oxygen for 5 days (vaso–obliteration period) followed by 5days in normoxia (relative ischemia period). Mice were treated with fluvastatin (10mg/Kg/day) or with saline during the time of exposure to high oxygen levels. Vascular obliteration was then evaluated by morphometric analysis using retinal flatmounts labeled with texas–red isolectin B4. Western blotting analysis was used to determine the retinal levels of vascular endothelial growth factor (VEGF). The malondialdheyde (MDA) technique was used to determine lipid peroxidation levels in the retinal extracts, as indicator of oxidative stress. Results: The morphometric analysis of retinal flatmounts showed that fluvastatin treatment significantly (p<0.05, n=14) reduced capillary dropout in the OIR retinas. Furthermore, the fluvastatin treatment significantly (p<0.01, n=14) prevented lipid peroxidation induced by the high oxygen treatment. Finally, retinal levels of the angiogenic cytokine vascular endothelial growth factor (VEGF) were decreased by the exposure to high oxygen levels and the statin treatment prevented this effect. Conclusions: Our results indicate that statin treatment effectively protects the developing retinal microvasculature during exposure to hyperoxic conditions and prevent oxygen–induced vascular drop–out. This effect is associated with decreased levels of oxidative stress and with preservation of normal expression levels of the endothelial cell survival factor VEGF.
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