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J. Aranda, E. Arnold, C. Vega-Cázares, J. Rivera, G. Martínez de la Escalera, C. Clapp; Vasoinhibins Inhibit Vascular Leakage and Vasodilation Induced by VEGF in the Retina. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3418.
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Vasoinhibins are a family of peptides derived from prolactin (PRL), growth hormone, and placental lactogen that act on endothelial cells to suppress vasodilation and angiogenesis via inhibition of endothelial nitric oxide synthase (eNOS). Here, we investigate whether vasoinhibins derived from PRL block VEGF-induced vascular permeability, vasodilation and NOS activity in the retina in vivo.
Vasoinhibins generated by enzymatic proteolysis of PRL or by recombinant DNA were injected intravitreally with or without VEGF. Twenty-four hours later, the retinas were dissected, and the flat-mounted retinal preparations were stained for blood vessels and digitized to evaluate vessel diameter and leakage areas. NOS activity was determined in retinal lysates by the [3H]L-citrulline method.
Intravitreal injection of VEGF increased the leakage area by seven fold and induced significant increases in vessel diameter (40%) and NOS activity (20%) in the retina. Treatment with vasoinhibins completely blocked the effects of VEGF.
Vasoinhibins reversed the VEGF- induced increases of NOS activity, vasopermeability, and vasodilation in the retina. These data suggest that vasoinhibins may have significant therapeutic potential for the treatment of diabetic macular edema and other VEGF-related ocular disorders.
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