Using patient-derived induced pluripotent stem cells-retinal pigment epithelium (iPSC-RPE) from AMD siblings, we discovered polarized cytokine secretion: apical IFN-β triggers photoreceptor apoptosis in human retinal organoids, while basal IL-17A compromises choroidal neovascularization. The gene discussed is IFNB1; the disease is age-related macular degeneration.