Therapeutic Effects Of Recombinant Heparin-Binding Domain (Hbd) Protein On Vegf-Induced Pathological Leukostasis And Angiogenesis In Mouse Models

Purpose: VEGF165 is the pathological VEGF isoform that causes retinal leukostasis in different rodent disease models including retinopathy of prematurity and diabetic retinopathy. Experimental evidence supports that the heparin-binding VEGF165 isoform, but not the VEGF121 isoform that lacks the heparin-binding domain (HBD), is responsible for inducing retinal leukostasis. Preliminary data from cell-based experiment suggest that the purified HBD protein can interfere with the pro-inflammatory activity VEGF165, likely by binding to the VEGF165 co-receptors heparan sulfate proteoglycans and neuropilins. We hypothesize that the HBD protein could be use to inhibit VEGF165-induced leukostasis and pathogenesis angiogenesis.Methods: Intravitreal injection of VEGF165 with and without recombinant HBD protein in wild type C57BL/6 mice was used for the leukostasis assay. Treated-eyes were perfused with …