PARP1 and dry age related macular degeneration: This study shows that the PARP-1-mediated necrotic pathway is distinct from that of the canonical parthanatos, serving as a novel mechanism of RPE loss in the pathogenesis of dry AMD: (1) PARP-1 is activated, leading to the death of ARPE-19 cells through mitochondrial dysfunction and cellular energy collapse in response to H2O2; (2) AIF, a typical downstream effector of PARP-1, does not participate in the execution of cell death in H2O2-induced ARPE-19 cells; (3) the essentiality of PARP-1 was validated in mouse and rabbit dry AMD models.