Age-related macular degeneration (AMD) is a major cause of blindness that is characterized by pathologic changes at the retinal pigment epithelium-choriocapillaris interface. We recently found that vascular loss of the choriocapillaris is relatedto 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. 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 in AMD. In this proposal we seek to identify the molecular and cellular responses of choroidal endothelial cells injured by MAC;to identify small molecules that protect choroidal endothelial cells against MAC-mediated lysis;and to develop and test avenues for the eventual replacement of lost endothelial cells. We anticipate that completion of these aims will result in important new understanding of mechanisms of protecting the choroid in early AMD, which may lead to new therapies for this blinding disease.

Public Health Relevance

Age-related macular degeneration is a devastating and common 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 injury by the immune system, how to rescue existing blood vessel cells from damage, and to develop methods to replace damaged blood vessels using stem cells.

National Institute of Health (NIH)
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Shen, Grace L
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University of Iowa
Schools of Medicine
Iowa City
United States
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Whitmore, S Scott; Sohn, Elliott H; Chirco, Kathleen R et al. (2015) Complement activation and choriocapillaris loss in early AMD: implications for pathophysiology and therapy. Prog Retin Eye Res 45:29-Jan
Whitmore, S Scott; Wagner, Alex H; DeLuca, Adam P et al. (2014) Transcriptomic analysis across nasal, temporal, and macular regions of human neural retina and RPE/choroid by RNA-Seq. Exp Eye Res 129:93-106