Exogenous mitochondrial transplantation attenuates oxidative stress-driven retinal degeneration in a sodium iodate -...

Age-related macular degeneration (AMD) is a degenerative retinal disease initiated by dysfunction of the retinal pigment epithelium (RPE), in which age-related mitochondrial impairment, oxidative stress, chronic inflammation, and complement activation collectively drive outer retinal dysfunction and RPE atrophy, ultimately leading to progressive central vision loss. Accumulating evidence indicates that mitochondrial abnormalities, including excessive reactive oxygen species (ROS) production, mitochondrial fragmentation, and inflammatory signaling, play a central role in AMD pathogenesis. In this study, we investigated the therapeutic potential of exogenous mitochondrial transplantation using a sodium iodate (SI)-induced retinal degeneration model that recapitulates key pathological features of dry AMD. In ARPE-19 cells, SI-induced oxidative stress triggered mitochondrial fragmentation, inflammasome activation, and tight junction disruption, whereas delivery of mitochondria isolated from bone marrow-derived mesenchymal stem cells attenuated mitochondrial dysfunction and preserved RPE barrier integrity by suppressing oxidative and inflammatory signaling. Consistent with these in vitro findings, intravitreal mitochondrial transplantation in SI-treated mice attenuated RPE shedding/migration and outer nuclear layer disorganization while suppressing retinal oxidative stress, inflammatory cytokine expression, and complement activation. Importantly, mitochondrial transplantation mitigated the decline in retinal function, as assessed by electroretinography and optokinetic response testing, without fully restoring responses to control levels. Collectively, these results support exogenous mitochondrial transplantation as a promising cell-free therapeutic strategy to attenuate oxidative stress-driven retinal degeneration by modulating mitochondrial dysfunction and associated inflammatory pathways in AMD.