selective inhibition of retinal angiogenesis by targeting pi3 kinase选择性抑制视网膜血管生成的目标pi3激酶.pdfVIP

Selective Inhibition of Retinal Angiogenesis by Targeting PI3 Kinase 1 1 2 1 1 Yolanda Alvarez *, Olaya Astudillo , Lasse Jensen , Alison L. Reynolds , Nora Waghorne , Derek P. 3 2 1 ´ 1 Brazil , Yihai Cao , John J. O’Connor , Breandan N. Kennedy * 1 UCD Schools of Biomolecular and Biomedical Sciences, UCD Conway Institute, University College Dublin, Dublin, Ireland, 2 Institute for Microbiology Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden, 3 Centre for Vision and Vascular Science, School of Medicine, Dentistry and Biomedical Science, Queen’s University Belfast, Belfast, United Kingdom Abstract Ocular neovascularisation is a pathological hallmark of some forms of debilitating blindness including diabetic retinopathy, age related macular degeneration and retinopathy of prematurity. Current therapies for delaying unwanted ocular angiogenesis include laser surgery or molecular inhibition of the pro-angiogenic factor VEGF. However, targeting of angiogenic pathways other than, or in combination to VEGF, may lead to more effective and safer inhibitors of intraocular angiogenesis. In a small chemical screen using zebrafish, we identify LY294002 as an effective and selective inhibitor of both developmental and ectopic hyaloid angiogenesis in the eye. LY294002, a PI3 kinase inhibitor, exerts its anti-angiogenic effect in a dose-dependent manner, without perturbing existing vessels. Significantly, LY294002 delivered by intraocular injection, significantly inhibits ocular angiogenesis without system