ABSTRACT
The human VEGF-A gene, located on chromosome 6p21.3, consists of eight exons and seven introns. Alternative splicing produces mRNA transcripts that code for at least six different protein isoforms: 121, 145, 165, 183, 189, and 206 amino acids in length (5). These different isoforms vary in their affi nity for heparin binding, and as such, in their affi nity for the extracellular matrix. The larger isoforms, such as VEGF189 and VEGF206, bind heparin with high affi nity, and are therefore almost completely sequestered in the extracellular matrix. The smaller isoform, VEGF121, does not bind heparin and is freely diffusible. All VEGF isoforms contain a plasmin cleavage site. Cleavage at this site creates a freely diffusible, 110 kDa, bioactive form of VEGF (VEGF110). Plasmin-mediated extracellular proteolysis may therefore be an important regulator of VEGF bioavailability (6). Further details on VEGF pathways in neovascular AMD can be found in chapter 4.
