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H Yamada, E Yamada, Y Yamazaki, M Matsumura; Inhibitory Effect of Angiotensin Converting Enzyme Inhibitors on Retinal Neovascularization . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1273.
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Purpose: Angiotensin Converting Enzyme Inhibitor (ACE-I) is used all over the world to control hypertension. Its clinical advantage is that it not only reduces blood pressure but also improves the prognosis of patients after cardiac or cerebral infarction by a vascular remodeling effect. There have been several reports on the anti-neovascular effects of ACE-I. We studied the efficacy of ACE-I on retinal neovascularization (NV). Methods: To induce retinal NV by hypoxic retinopathy, C57bl mice were kept under 75% oxygen for 5 days, from P7 to P12, then moved to a normoxic environment for 5 days. We administered 30 mg/kg Atenolol (b blocker), 30 mg/kg Amlodipine (Ca blocker), 20 mg/kg Enalapril (ACE-I), 2 mg/ml Perindopril (ACE-I), 20 mg/kg Perindopril, or vehicle only (dH2O) to the mice once a day for 5 days. Animals were sacrificed at P17 and perfused with fluorescein dextran through the left ventricle before enucleation or were enucleated immediately, and the eyes were prepared for cryotome sectioning. Fluorescein-dextran-perfused eyeballs were fixed in buffered formalin. Retinae were dissected, flat-mounted on slide glass, and observed under a fluorescein microscope. Non-perfusion areas (NPA) were evaluated using ImagePro software. Cryo-sectioned eyeballs were stained immunohistochemically by Griffonia simpliciforia isolectin-B4 and the NV beneath the retina was evaluated. Results: Mice administered Atenolol, Amlodipine, and vehicle only showed large NPA in the retina and massive retinal NV of almost the same size.Mice administered Enalapril, 2 mg/kg Perindopril, and 20 mg/kg Perindopril showed a smaller amount of NV than the other groups. In particular, 20 mg/kg Perindopril showed 80% inhibition of retinal NV (p<0.001). NPA in the Enalapril and 2 mg/kg Perindopril groups were the same size as those in the Atenolol, Amlodipine, and vehicle groups, but the 20 mg/kg Perindopril group showed much smaller NPA (p=0.001). Conclusion: ACE-I, and especially a high dose of Perindopril, inhibited retinal NV. ACE-I has a direct inhibitory effect on retinal NV and inhibits NV more intensely by reperfusing the retinal NPA when it is administered at a high dose.
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