An antisense oligodeoxynucleotide against vascular endothelial growth factor in a nonhuman primate model of iris neovascularization

Objective: To evaluate an antisense oligodeoxynucleotide (AS-ODN) targeted against vascular endothelial growth factor for its effects on ocular angiogenesis and its intraocular localization in a nonhuman primate model of iris neovascularization. Methods: Bilateral laser retinal vein occlusion was performed in monkeys, followed by intravitreal injections of a vascular endothelial growth factor-specific AS-ODN or control. Serial fluorescein angiograms were graded in a masked manner to measure iris neovascularization. Localization was determined using a fluorescent-labeled AS-ODN and confocal microscopy on fixed tissue. Results: Intravitreally injected vascular endothelial growth factor-specific AS-ODN localized to the retina, in the ganglion cell layer, inner nuclear layer, outer plexiform layer, photoreceptor outer segments, and retinal pigment epithelium. In 8 animals tested with 3muM ODN, AS-ODN-treated eyes had a significant reduction in iris neovascularization compared with control fellow eyes (P = .006, MIXOR analysis). Overall, in 17 animals tested across a range of ODN concentrations (0.1-50.0muM), AS-ODN-treated eyes were more likely to have lower iris neovascularization grades (P = .006, McNemar test) and the absence of iris neovascularization (P < .001, mixed-effects logistic regression model). Conclusion: Antisense ODNs that target vascular endothelial growth factor delivered to the retina via intravitreal injection reduced iris neovascularization in this model. Clinical Relevance: Antisense ODNs against vascular endothelial growth factor may have therapeutic potential for neovascular eye diseases.