CFH Loss in Human RPE Cells Leads to Inflammation and Complement System Dysregulation via the NF-κB Pathway

Age-related macular degeneration (AMD), the leading cause of vision loss in elderly, is a degenerative disease macula, where retinal pigment epithelium (RPE) cells are damaged early stages disease, and chronic inflammatory processes may be involved. Besides aging lifestyle factors as drivers AMD, strong genetic association to AMD found genes complement system, with single polymorphism factor H gene (CFH), accounting for majority risk. However, exact mechanism CFH dysregulation confers such great risk its role RPE cell homeostasis unclear. To explore endogenous locally cells, we silenced human hTERT-RPE1 cells. We demonstrate that endogenously expressed modulates cytokine production regulation, independent external sources, or stressors. show protein (FH) results increased levels mediators (e.g., IL-6, IL-8, GM-CSF) altered proteins C3, CFB upregulation, C5 downregulation) known play AMD. Moreover, our identify NF-κB pathway major involved regulating these factors. Our findings suggest FH work synergy maintain balance, case either one them dysregulated, microenvironment changes towards proinflammatory AMD-like phenotype.