Complement System and Choroidal Neovascularization

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DESCRIPTION (provided by applicant): The complement system plays a critical role in the host defense against microorganisms and in the modulation of inflammatory responses. Recently, it has been suggested that there may be a link between complement activation and vascular proliferation. Age-related macular degeneration (ARMD) is the leading cause of blindness in the Western world in individuals over 55 years of age. Although the nonexudative (dry) form of ARMD is more prevalent, catastrophic vision loss is more frequently associated with the exudative (wet) form, specifically from the complications of neovascularization of the choroid. The pathogenesis of new choroidal vessel formation (CNV) in exudative ARMD is poorly understood. Although inflammation has been implicated in the development of CNV the role of complement has not been explored. In the current proposal we wish to explore the role of complement in choroidal neovascularization using the mouse model of laser-induced CNV. Using this model, our recent results suggest that the complement system is central to the development of laser-induced choroidal angiogenesis. Thus, we propose to explore the role of complement and complement regulatory proteins in the development of experimental CNV, as well as the treatment effect of complement inhibition using soluble complement regulatory proteins. The specific aims of this proposal are: 1. To study the complement system in the mouse model of laser-induced CNV. 2. To study complement regulatory proteins (CRPs) in the mouse model of laser-induced CNV. 3. To establish the complement (i.e. MAC) dependence and temporal expression of angiogenic growth factors in laser-induced CNV. We believe that these studies will lead to a better understanding of an important underlying molecular mechanism in the development of CNV (i.e. complement activation), and will help to identify new molecular targets for novel therapeutic approaches.