Mitochondrial transplantation attenuates oligomeric amyloid-beta-induced mitochondrial dysfunction and tight junction protein destruction in retinal pigment epithelium

• Published in: Free radical biology & medicine Vol. 212; pp. 10 - 21
• Main Authors: Noh, Sung-Eun, Lee, Seok Jae, Cho, Chang Sik, Jo, Dong Hyun, Park, Kyu Sang, Kim, Jeong Hun
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 20.02.2024
• Subjects: Age-related macular degeneration; Amyloid beta-Peptides - genetics; Amyloid beta-Peptides - metabolism; Animals; Mesenchymal stem cells; Mice; Mitochondria - metabolism; Mitochondrial Diseases - metabolism; Mitochondrial transplantation; Oligomeric amyloid-beta; Reactive oxygen species; Retinal Pigment Epithelium - metabolism; Tight junction proteins; Tight Junction Proteins - metabolism; Reactive oxygen species; Mitochondrial transplantation; Oligomeric amyloid-beta; Age-related macular degeneration; Tight junction proteins; Mesenchymal stem cells
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2023.12.012

Transplantation of mitochondria derived from mesenchymal stem cells (MSCs) has emerged as a new treatment method to improve mitochondrial dysfunction and alleviate cell impairment. Interest in using extrinsic mitochondrial transplantation as a therapeutic approach has been increasing because it has been confirmed to be effective in treating various diseases related to mitochondrial dysfunction, including ischemia, cardiovascular disease, and toxic damage. To support this application, we conducted an experiment to deliver external mitochondria to retinal pigment epithelial cells treated with oligomeric amyloid-beta (oAβ). Externally delivered amyloid-beta internalizes into cells and interacts with mitochondria, resulting in mitochondrial dysfunction and intracellular damage, including increased reactive oxygen species and destruction of tight junction proteins. Externally delivered mitochondria were confirmed to alleviate mitochondrial dysfunction and tight junction protein disruption as well as improve internalized oAβ clearance. These results were also confirmed in a mouse model in vivo. Overall, these findings indicate that the transfer of external mitochondria isolated from MSCs has potential as a new treatment method for age-related macular degeneration, which involves oAβ-induced changes to the retinal pigment epithelium. [Display omitted] •Oligomeric Amyloid-beta (oAβ) is a potential pathogenic factor of AMD.•Extracellular oAβ internalized causes mitochondrial dysfunction and cellular damage.•Extrinsic mitochondria improve internalized amyloid-beta clearance.•Mitochondrial dysfunction and cellular impairment attenuate upon extrinsic mitochondrial transplantation.•Exogenous mitochondrial delivery is a plausible therapeutic approach for AMD treatment.