Abstract：
:Nitric oxide (NO) promotes retinal and choroidal neovascularization, although different isoforms of nitric-oxide synthetase (NOS) are critical in each. Deficiency of endothelial NOS (eNOS) suppresses retinal but not choroidal neovascularization, whereas deficiency of neuronal NOS (nNOS) or inducible NOS (iNOS) suppresses choroidal, but not retinal neovascularization. In this study, we investigated the effect of N(G)-monomethyl-L-arginine (L-NMMA), a nonspecific NOS inhibitor, in three models of ocular neovascularization. Oral administration of L-NMMA caused significant inhibition of choroidal neovascularization in mice with laser-induced rupture of Bruch's membrane and significantly inhibited subretinal neovascularization in transgenic mice with expression of vascular endothelial growth factor (VEGF) in photoreceptors (rho/VEGF mice) but did not inhibit retinal neovascularization in mice with ischemic retinopathy. By extensive mating among mice deficient in NOS isoforms, triple homozygous mutant mice deficient in all three NOS isoforms were produced. These mice had marked suppression of choroidal neovascularization at sites of rupture of Bruch's membrane and near-complete suppression of subretinal neovascularization in rho/VEGF mice but showed no difference in ischemia-induced retinal neovascularization compared with wild-type mice. These data indicate that NO is an important stimulator of choroidal neovascularization and that reduction of NO by pharmacologic or genetic means is a good treatment strategy. However, the situation is more complex for ischemia-induced retinal neovascularization for which NO produced in endothelial cells by eNOS is stimulatory, but NO produced in other retinal cells by iNOS and/or nNOS is inhibitory. Selective inhibitors of eNOS may be needed for treatment of retinal neovascularization.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Ando A,Yang A,Nambu H,Campochiaro PAdoi
10.1124/mol.62.3.539keywords:
subject
Has Abstractpub_date
2002-09-01 00:00:00pages
539-44issue
3eissn
0026-895Xissn
1521-0111journal_volume
62pub_type
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pub_type： 杂志文章
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journal_title：Molecular pharmacology
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journal_title：Molecular pharmacology
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更新日期：1995-12-01 00:00:00
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pub_type： 杂志文章
doi：
更新日期：1982-05-01 00:00:00
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pub_type： 杂志文章
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1987-01-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
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更新日期：1993-10-01 00:00:00
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pub_type： 杂志文章
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pub_type： 杂志文章,评审
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journal_title：Molecular pharmacology
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journal_title：Molecular pharmacology
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pub_type： 杂志文章
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更新日期：2006-09-01 00:00:00
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pub_type： 杂志文章,评审
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更新日期：2009-07-01 00:00:00
