Retinal pigment epithelium (RPE) damage is a major factor in age-related macular degeneration (AMD). The RPE in AMD shows mitochondrial dysfunction suggesting an association of AMD with mitochondrial function. Therefore, exogenous mitochondrial transplantation for restoring and replacing dysfunctional mitochondria may be an effective therapeutic strategy for AMD. Here, we investigated the effects of extrinsic mitochondrial transplantation on senescence-induced ARPE-19 cells. We demonstrated mitochondrial dysfunction in replicative senescence-induced ARPE-19 cells after repeated passage. Imbalanced mitophagy and mitochondrial dynamics resulted in increased mitochondrial numbers and elevated levels of mitochondrial and intracellular reactive oxygen species. Exogenous mitochondrial transplantation improved mitochondrial dysfunction and alleviated cellular senescence hallmarks, such as increased cell size, increased senescence-associated β-galactosidase activity, augmented NF-κB activity, increased inflammatory cytokines, and upregulated the cyclin-dependent kinase inhibitors p21 and p16. Further, cellular senescence properties were improved by exogenous mitochondrial transplantation in oxidative stress-induced senescent ARPE-19 cells. These results indicate that exogenous mitochondrial transplantation modulates cellular senescence and may be considered a novel therapeutic strategy for AMD.
|Number of pages||9|
|Journal||Neurobiology of Aging|
|Publication status||Published - 2023 Jan|
Bibliographical noteFunding Information:
This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) ( 2015M3A7B6027946 to J.H. Kim), the Development of Platform Technology for Innovative Medical Measurement funded by Korea Research Institute of Standards and Science ( KRISS-GP2022-0006 to J.H. Kim) and Kun-hee Lee Child Cancer & Rare Disease Project, Republic of Korea ( 202200004004 to J.H. Kim).
© 2022 Elsevier Inc.
All Science Journal Classification (ASJC) codes
- Clinical Neurology
- Developmental Biology
- Geriatrics and Gerontology