Age-related increases in amyloid beta and membrane attack complex: evidence of inflammasome activation in the rodent eye

摘要: The membrane attack complex (MAC) is a key player in the pathogenesis of age-related macular degeneration (AMD) and putative activator NLRP3 inflammasome. Amyloid beta (Aβ), component drusen deposits, has also been implicated inflammasome activation by our work those others. However, interactions MAC Aβ are still poorly understood, especially their roles aging retinal degenerative pathologies. Since may represent cellular pathway underlying chronic inflammation eye, purpose this study to identify effects associated with pigment epithelium (RPE)/choroid evaluate therapeutic merits suppression. Adult Long-Evans rats were divided into treatment control groups. Treatment groups received oral aurin tricarboxylic acid (ATAC), inhibitor, drinking-water, drinking-water alone (No ATAC). Groups sacrificed at 7.5 or 11.5 months, after approximately 40 days ATAC treatment. To changes RPE/choroid, naive animals 2.5, 7.5, 11.5 months. Eye tissues underwent immunohistochemistry western blot analysis for MAC, Aβ, NF-κB activation, as well cleaved caspase-1 IL-18. Vitreal samples collected assessed multiplex assays secreted levels IL-18 IL-1β. Statistical analyses performed, significance level was set p ≤ 0.05. In vivo studies demonstrated an age-dependent increase RPE/choroid. Systemic resulted prominent reduction formation concomitant measured IL-1β, but not activation. vitro Aβ-induced on RPE cells. Age-dependent increases present rodent outer retina. Our results suggest that suppressing subsequent RPE/choroid reduce low-grade IL-1β