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H. Yamada, E. Yamada, A. Higuchi, M. Matsumura; Inhibitory Effect of Quinapril on Retinal and Choroidal Neovascularization . Invest. Ophthalmol. Vis. Sci. 2003;44(13):552.
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Purpose: Angiotensin converting Enzyme Inhibitor (ACE-I) is commonly used for hypertension in patients. Its clinical advantages include reduction of blood pressure and improved prognosis in patients suffering cardiac or cerebral infarction. We previously reported the anti-neovascular effect of Perindopril. We studied the efficacy of Quinapril, a stronger ACE inhibitor than Perindopril, 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, and then moved to a normal environment for 5 days. These animals, were given 20, 50mg/kg Quinapril or vehicle only (dH2O) once a day for 5 days. Animals were sacrificed at P17 and perfused with fluorescein dextran via the left ventricle before enucleation, or enucleated immediately and prepared for cryotome sectioning. Fluorescein-dextran-perfused eyeballs were fixed in buffered formallin. Retinae were dissected, flat mounted on slides, and observed by fluorescence microscopy. Non-perfused areas (NPA) were evaluated using ImagePro Plus software. Cryo-sectioned eyeballs were stained immunohistochemically with gliffonia simpliciforia isolectin-B4 and the NV beneath the retina were evaluated. To induce experimental CNV, adult C57bl mice were anesthetized and treated with Krypton laser to break Bruch's membrane. Thereafter we administered 50mg/kg Quinapril, or vehicle only (dH2O) once a day for 14 days. At day 14, eyeballs were enucleated and fixed in buffered formallin. Under dissection microscope, the posterior portion of the eye was isolated, flat mounted choroidal side up and observed by fluorescence microscopy. Areas of CNV were evaluated using ImagePro software. Results: Mice given Quinapril and vehicle only showed large NPA in the retina. The 50mg/kg Quinapril group showed statistically larger NPA. Mice given Quinapril showed less NV compared to those given vehicle only. Quinapril had no effect on CNV. Conclusions: Quinapril had an inhibitory effect on retinal NV, but not on CNV. In our former study, Perindopril inhibited both retinal and choroidal NV. These results suggest that the inhibitory effect on ocular NV by ACE-I is not determined by its ability to inhibit ACE.
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