Nitric oxide is proangiogenic in the retina and choroid.
Nitric oxide (NO) has been shown to have proangiogenic or antiangiogenic effects depending upon the setting. In this study, we used mice with targeted deletion of one of the three isoforms of nitric oxide synthase (NOS) to investigate the effects of NO in ocular neovascularization. In transgenic mice with increased expression of vascular endothelial growth factor (VEGF) in photoreceptors, deficiency of any of the three isoforms caused a significant decrease in subretinal neovascularization, but no alteration of VEGF expression. In mice with laser-induced rupture of Bruch's membrane, deficiency of inducible NOS (iNOS) or neuronal NOS (nNOS), but not endothelial NOS (eNOS), caused a significant decrease in choroidal neovascularization. In mice with oxygen-induced ischemic retinopathy, deficiency of eNOS, but not iNOS or nNOS caused a significant decrease in retinal neovascularization and decreased expression of VEGF. These data suggest that NO contributes to both retinal and choroidal neovascularization and that different isoforms of NOS are involved in different settings and different disease processes. A broad spectrum NOS inhibitor may have therapeutic potential for treatment of both retinal and choroidal neovascularization.
Ando
Akira
A
Department of Ophthalmology, The Johns Hopkins University School of Medicine, Maumenee, N. Wolfe Street, Baltimore, Maryland 21287-9277, USA.
Yang
Amy
A
Mori
Keisuke
K
Yamada
Haruhiko
H
Yamada
Eri
E
Takahashi
Kyoichi
K
Saikia
Jina
J
Kim
Min
M
Melia
Michele
M
Fishman
Mark
M
Huang
Paul
P
Campochiaro
Peter A
PA
D000818:Animals; D016570:Bruch Membrane / Q000528:radiation effects; D002829:Choroid / Q000098:blood supply*; D007511:Ischemia / Q000503:physiopathology; D007834:Lasers; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D009389:Neovascularization, Pathologic / Q000209:etiology*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000172:deficiency / Q000235:genetics; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D012171:Retinal Vessels
D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496321:Nos1 protein, mouse; C496317:Nos2 protein, mouse; C496315:Nos3 protein, mouse