Microarray Analysis Identifies Changes in Inflammatory Gene Expression in Response to Amyloid-β Stimulation of Cultured Human Retinal Pigment Epithelial Cells

摘要: Age-related macular degeneration (AMD) is the most common cause of irreversible vision loss in elderly. The disease characterized by extracellular deposits known as drusen, which are found between basal lamina retinal pigment epithelium (RPE) and inner layer Bruch’s membrane (BM). Although, presence drusen correlates with development AMD, specific mechanisms underlying biogenesis its relationship to remain elusive.1–3 Extensive biochemical analysis revealed several proteins linked inflammation. Such include immunoglobulins, acute-phase molecules (vitronectin, amyloid P, fibrinogen), complement factors (C5 C5b-9), regulatory (clusterin receptor 1).4–8 These findings implicate an inflammatory process associated but what activates or triggers inflammation remains unknown.4,9–12 Several lines evidence suggest that amyloid-β1-40 (Aβ1-40), a constituent potential candidate trigger peptide.3,13–15 Genetically modified mice increased Aβ deposition display many traits consistent human such accumulation sub-RPE deposits, microglial activation, neurons RPE.16,17 In retina, cell types including neurons, RPE, glia may provide local source species; they have been shown cellular machinery for synthesis precursor protein (APP) cleavage enzymes.10 Sequential APP processing β- γ-secretase produces major species, Aβ1-40. Recent vitro studies RPE cells stimulated Aβ1-40 demonstrated results proinflammatory response. Wang et al.18 reported stimulation caused abnormal activity factor I (CFI), inhibitory regulator cascade. another study, modulated expression vascular endothelial growth (VEGF), promote angiogenesis, late-stage feature AMD.17 prompted us further elucidate effects on differential microarrays corresponding functional pathway analysis. We hypothesize promotes gene changes pathways implicated pathogenesis oxidative stress, inflammation, apoptosis.