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Description
Age related macular degeneration (AMD) is the leading cause of irreversible blindness in
industrialized nations, affecting 30-50 million people worldwide. The earliest clinical hallmark
of AMD is the presence of drusen, extracellular deposits that accumulate beneath the retinal
pigmented epithelium (RPE). Although drusen nearly always precede and increase the risk of
choroidal neovascularization (CNV), the late vision-threatening stage of AMD, it is not known
whether drusen contribute to the development ofCNV. Both in patients with AMD and in a
recently described mouse model, early sub-RPE deposition of complement components C3 and
C5 has been demonstrated, suggesting a contributing role for these inflammatory proteins in the
development of AMD. Here we show that C3 and C5 induce vascular endothelial growth factor
(VEGF) expression in vivo. Further we demonstrate that C3 and C5 are expressed early in the
course oflaser-induced CNV, an accelerated model ofneovascular AMD driven by VEGF and
recruitment of leukocytes into the choroid. We also show that genetic ablation of receptors for
activated C3 and C5 reduces VEGF expression, leukocyte recruitment, and CNV formation
following laser injury. Collectively these findings establish a mechanistic basis for the clinical
observation that drusen predispose to CNV, both revealing a novel role for immunological
phenomena in angiogenesis and providing new therapeutic targets for AMD.
Status | Finished |
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Effective start/end date | 6/1/04 → 5/31/10 |
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