The Role of SPARC in Macular Propensity for CNV

Project Summary

Age-related macular degeneration is as common as cancer in the United States. The principal cause of vision loss AMD is choroidal neovascularization (CNV), the growth of abnormal blood vessels (angiogenesis) beneath the retina. CNV is devastating because it occurs almost always in the macula, the central retina that provides fine vision. The reason for this macular propensity is unknown. We have identified a protein called SPARC that is present almost exclusively in the macula and increased in AMD. We have also shown that the presence of SPARC is necessary for VEGF-A, a potent molecule that promotes angiogenesis, to perform this function. We have also shown that the presence or absence of SPARC determines whether VEGF-A acts via VEGF receptor-1, which suppresses angiogenesis, or VEGF receptor-2, which promotes angiogenesis. We will determine the levels of SPARC, VEGF-A and the activity of VEGF receptors in the macula and peripheral retina in patients with or without AMD, and whether blocking SPARC reduces CNV in animal models. We will determine whether the differential distribution of SPARC underlies the macular propensity of CNV and whether modulating SPARC will reduce the attractiveness of the macula for CNV development, thereby permitting improved vision in patients with AMD.