Ando A, Yang A, Mori K, Yamada H, Yamada E, Takahashi K, Saikia J, Kim M, Melia M, Fishman M, Huang P, Campochiaro PA. 2002. Nitric oxide is proangiogenic in the retina and choroid. Journal of cellular physiology. 191(1):116-24. Pubmed: 11920687


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.
Copyright 2002 Wiley-Liss, Inc.

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Photo of Mark C. Fishman

Mark C. Fishman’s group studies the heart-brain connection. They employ a range of genetic, developmental, and neurobiological tools in zebrafish to understand what the heart tells the brain, and how critical internal sensory systems adjust homeostatic and somatic behaviors, including social interactions.

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