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S. Wasmuth, K. Lueck, A. Lommatzsch, D. Pauleikhoff; Complement enhances the Vitronectin Production of Retinal Pigment Epithelial Cells. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4177.
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Age-related macular degeneration (AMD) seems connected with more activated complement on the alternative pathway and the extracellular matrix component vitronectin is highly observed in drusen and surgically excised neovascular membranes. In this study the influence of complement on the vitronectin production by retinal pigment epithelial (RPE) cells was evaluated.
ARPE-19 cells were cultivated with increasing amounts of lipopolysaccharide (LPS) as unspecific stimulation and with human serum as complement source in its naïve and heat inactivated form. In another series of experiments zymosan as an activator of the alternative pathway of complement was tested alone and in combination with naïve human serum. Vitronectin was assayed in situ by immunohistochemistry, on protein level by western blot and by PCR after reverse transcription of total RNA.
A constitutive production of vitronectin by RPE cells was detected by all three tests. With naïve human serum more vitronectin was found by immunohistochemistry and western blot while the number of mRNA transcripts was not significantly altered. The vitronectin production was further enhanced with the combination of zymosan and naïve human serum. LPS did not alter the vitronectin production by RPE cells.
Activated complement lead to an increased vitronectin production by RPE cells on post-transcriptional level. Enhanced complement activation during AMD might also contribute in vivo to an enhanced production of vitronectin by RPE cells. This can cause thickening of Bruch’s membrane and may play a role in the development of drusen.
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