Age-related macular degeneration (AMD) is a major cause of blindness worldwide that is characterized by pathologic changes at the retinal pigment epithelium-choriocapillaris interface. We recently found that loss of endothelial cells of the choriocapillaris is related to the earliest clinical signs of AMD, and that a reduced vascular density and increased number of ?ghost? vessels are related to the size and number of drusen and other subRPE deposits. Compelling evidence suggest that activation of the terminal complement pathway and formation of the membrane attack complex (MAC) at the level of the choriocapillaris is a likely cause of vascular loss and AMD pathogenesis. In this proposal we seek to identify the molecular and cellular responses of choroidal endothelial cells injured by MAC; to evaluate small molecules that protect choroidal endothelial cells against MAC-mediated lysis; and to develop an autologous iPSC based choroidal endothelial cell replacement approach. We anticipate that completion of the aims outlined in this application will result in an important new understanding of disease pathophysiology, which will allow us to further develop treatments focused on protecting and replacing damaged blood vessels in AMD.
Age-related macular degeneration is a common devastating disease that can lead to blindness. We recently found that loss of blood vessels appears to play an important role in the earliest stages of macular degeneration. The goal of this research program is to pursue new treatments for AMD by determining how blood vessel cells respond to immune injury, how to rescue existing blood vessel cells from damage, and to develop methods to replace damaged blood vessels using stem cells.
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