VEGF165 (vascular endothelial growth factor-165), is a member of the VEGF family that promotes angiogenesis by stimulating endothelial cell proliferation and migration. The VEGF gene is located on human chromosome 6 and alternative splicing of VEGF mRNA accounts for at least six different isoforms from a single gene. VEGF is a signal protein that is known to regulate angiogenesis in physiologically important events such as fetal development and wound repair. It is also implicated in pathologic disorders associated with angiogenesis such as tumor growth. VEGF has many isoforms, and one of them known as VEGF165 is primarily responsible for ocular neovascularization, which often results in a serious eye disease such as age-related macular degeneration (AMD). The VEGF isoforms differ in their heparin-binding properties, membrane association and secretion; VEGF 121 and 165 are the only freely soluble isoforms as the other isoforms are predominantly bound to heparin in the extracellular matrix.. In vivo, only the three secreted isoforms, VEGF 121, 145 and 165, induce angiogenesis, with VEGF 165 being the predominant isoform that is secreted by benign and malignant cells .VEGF165 is composed of the heparin binding domain (HBD) and the receptor binding domain (RBD) which are connected by a flexible linker.8 The structure of each domain has been determined, but mainly due to the flexible linker, the whole VEGF165 structure has not been determined. VEGF is the most significant growth factor that controls angiogenesis in normal and tumor cells. VEGF has been identified as a heparin-binding angiogenic growth factor, which exhibits high specificity for endothelial cells. In the central nervous system, VEGF165 can also act as a neuroactive factor by inducing neurogenesis as well as neural progenitor cell (NPC) proliferation.