Inhibition of rat corneal angiogenesis by a nuclease-resistant RNA aptamer specific for angiopoietin-2.
Angiopoietin-2 (Ang2) appears to be a naturally occurring antagonist of the endothelial receptor tyrosine kinase Tie2, an important regulator of vascular stability. Destabilization of the endothelium by Ang2 is believed to potentiate the actions of proangiogenic growth factors. To investigate the specific role of Ang2 in the adult vasculature, we generated a nuclease-resistant RNA aptamer that binds and inhibits Ang2 but not the related Tie2 agonist, angiopoietin-1. Local delivery of this aptamer but not a partially scrambled mutant aptamer inhibited basic fibroblast growth factor-mediated neovascularization in the rat corneal micropocket angiogenesis assay. These in vivo data directly demonstrate that a specific inhibitor of Ang2 can act as an antiangiogenic agent.
White
Rebekah R
RR
Department of Surgery, Duke University Medical Center, Durham, NC 22710, USA.
Shan
Siqing
S
Rusconi
Christopher P
CP
Shetty
Geetha
G
Dewhirst
Mark W
MW
Kontos
Christopher D
CD
Sullenger
Bruce A
BA
D043925:Angiogenesis Inducing Agents / Q000235:genetics* / Q000378:metabolism; D042702:Angiopoietin-2; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003315:Cornea / Q000098:blood supply*; D017931:DNA Primers; D005260:Female; D006801:Humans; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D011233:Precipitin Tests; D011485:Protein Binding; D012313:RNA / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344
D043925:Angiogenesis Inducing Agents; D042702:Angiopoietin-2; D017931:DNA Primers; D012313:RNA