Mitophagy-Inducing Nanocarriers Restore Mitochondrial Quality and Cell Functions in Senescent Retinal Pigment Epithelial Cells

Age-related macular degeneration (AMD) is an age-associated disease characterized by damage to the central retina and represents a leading cause of acquired blindness, with increasing prevalence in aging populations. However, effective therapeutic options remain limited. The accumulation of dysfunctional mitochondria in retinal pigment epithelial (RPE) cells leads to excessive production of reactive oxygen species (ROS), triggering cellular senescence and cell death that contribute to the pathogenesis of AMD. Therefore, removal of accumulated dysfunctional mitochondria in senescent RPE cells is expected to treat AMD. Herein, we investigated transferrin (Trf)-modified mitophagy-inducing dual-drug nanocarriers (Trf-M-NCs) for the treatment of a senescent RPE cell. To evaluate efficacy, we used sodium iodate-treated ARPE-19 cells. The Trf-M-NCs exhibited significantly higher uptake by ARPE-19 cells than the unmodified M-NCs. Importantly, Trf-M-NC treatment alleviated cellular senescence by restoring the mitochondrial functions. Furthermore, Trf-M-NC treatment not only restored the production of α-ketoglutarate, an essential energy source for photoreceptor cells, but also reduced the secretion of IL-6, a key inflammatory cytokine. These findings suggest that improving mitochondrial quality in RPE cells is a novel and promising therapeutic approach for AMD.