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J. M. Skeie, J. Hernandez, R. F. Mullins; Chorioretinal Endothelial Cell Responses to Elastin Fragments. Invest. Ophthalmol. Vis. Sci. 2010;51(13):6178.
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Elevated elastin fragments promote choroidal endothelial cells to increase migration, a key event in neovascular age-related macular degeneration (AMD). Our current investigation aims to determine the effects of elevated elastin fragments in vivo and to identify the possible endothelial cell receptor(s) responsible for this activity.
Migration of the chorioretinal endothelial cell line RF/6A in response to elastin peptides was assessed in the presence of inhibitors of two elastin receptors, ITGAV/ITGB3 and GLB1. Albino C57/BL 6 mice were injected intraperitoneally with elastin fragments or control saline 3x weekly for one month. Changes in whole eye gene expression were determined using microarray analysis and ultrastructural observations were performed using TEM.
Blocking either ITGAV/ITGB3 or GLB1 reduced the migration of chorioretinal endothelial cells back to baseline levels. Eyes of mice injected with elastin fragments had a greater than 50% increase in expression of 20 genes including Ceacam10, Ces7, Hspb1, Pacsin3, and Col4a2 (p-values < 0.01). No major ultrastructural differences were detected in eyes of mice injected with elastin fragments compared to control eyes.
Chorioretinal endothelial cells increase migration in the presence of elastin fragments and this response is inhibited by both GLB1 and ITGAV/ITGB3 antagonists, indicating that both proteins may be endothelial cell receptors for elastin peptides. In vivo, elastin fragments cause a significant increase in the transcription of genes which may play a role in pathways associated with AMD. Determining the mechanism by which elastin peptides bind to and activate choroidal endothelial cells will further our understanding of AMD pathology.
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