The present invention is directed to methods for developing novel anti-angiogenic therapies. This invention discovers secretogranin III (Scg3) not only as a novel disease-selective angiogenic factor but also as a target for anti-angiogenic therapy of vascular diseases. Inhibitors against Scg3 can treat diabetic retinopathy, wet age-related macular degeneration, retinopathy of prematurity, retinal vein occlusion, neovascular glaucoma, corneal neovascularization, and cancers.