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(American Journal of Pathology. 2004;165:2177-2185.)
© 2004 American Society for Investigative Pathology

Inhibition of Ocular Angiogenesis by siRNA Targeting Vascular Endothelial Growth Factor Pathway Genes

Therapeutic Strategy for Herpetic Stromal Keratitis

Bumseok Kim^*, Qingquan Tang, Partha S. Biswas^*, Jun Xu, Raymond M. Schiffelers, Frank Y. Xie, Aslam M. Ansari, Puthupparampil V. Scaria, Martin C. Woodle, Patrick Lu and Barry T. Rouse^*

From Comparative and Experimental Medicine,^* College of Veterinary Medicine, University of Tennessee, Knoxville, Tennessee; and the Department of Genomics and Therapeutics, Intradigm Corporation, Rockville, Maryland

Ocular neovascularization often results in vision impairment. Frequently vascular endothelial cell growth factors (VEGFs) are mainly responsible for the pathological neovascularization as in the case in neovascularization induced by CpG oligodeoxynucleotides and herpes simplex virus infection in this report. siRNAs targeting either VEGFA, VEGFR1, VEGFR2, or a mix of the three were shown to significantly inhibit neovascularization induced by CpG when given locally or systemically. The efficacy of systemic administration was facilitated by the use of a polymer delivery vehicle. Additional experiments showed a significant inhibitory effect of the siRNAs mix when given either locally or systemically in vehicle against herpes simplex virus-induced angiogenesis as well as against lesions of stromal keratitis. These results indicate that the use of VEGF pathway-specific siRNAs represents a useful therapy against neovascularization-related eye diseases.

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