Sub-lytic C5b-9 induces functional changes in retinal pigment epithelial cells consistent with age-related macular degeneration

作者: K Lueck , S Wasmuth , J Williams , T R Hughes , B P Morgan

DOI: 10.1038/EYE.2011.109

关键词:

摘要: PURPOSE: There is evidence for complement dysfunction in age-related macular degeneration (AMD). Complement activation leads to formation of the membrane attack complex (MAC), known assemble on retinal pigment epithelial (RPE) cells. Therefore, effect sub-lytic MAC RPE cells was examined with regard pro-inflammatory or pro-angiogenic mediators relevant AMD. METHODS: For induction, were incubated an antiserum regulatory protein CD59, followed by normal human serum (NHS) induce 5% cell death, measured a viability assay. evaluated immunofluorescence and FACS analysis. Interleukin (IL)-6, -8, monocytic chemoattractant protein-1 (MCP-1), vascular endothelial growth factor (VEGF) quantified enzyme-linked immunosorbent assay (ELISA). Intracellular MCP-1 analysed immunofluorescence, vitronectin western blotting, gelatinolytic matrix metalloproteinases (MMPs) zymography. RESULTS: Incubation CD59 NHS induced amounts MAC, verified immunofluorescence. This treatment stimulated release IL-6, MCP-1, VEGF. staining, production vitronectin, MMPs also elevated response MAC. CONCLUSIONS: assembly increases production. might have significant role generating microenvironment, contributing development AMD. Enhanced be protective mechanism against deposition. In addition, increased expression VEGF may associated neovascular processes late

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