The present study demonstrated that NMN treatment could ameliorate the cellular senescence and retinal inflammation caused by NaIO3 exposure. This protective effect was executed upon NAD+ supplementation, which enhanced mitochondrial function, reduced DNA damage, and suppressed the activation of AMPK and Akt/mTOR signalling. NMN treatment also maintained the hexagonal structure of RPE in vivo and reduced senescence-related retinal inflammation. Moreover, undisturbed Sirt1 activity was required for NMN to exert its antisenescent effects. Overall, our results provided novel insights into the pathogenesis of age-related macular degeneration (AMD) and a potential therapeutic strategy for AMD from the perspective of cellular and histological senescence.