Mitochondrial transplantation protects the retinal pigment epithelial cells from the oxidative stress induced by NaIO3.

The retinal pigment epithelium (RPE) is the outermost part of the retina, and it is essential for the photoreceptor survival and function. Oxidative stress, aging, accumulation of lipofuscin, and drusen can lead to retinal degenerative diseases such as age-related macular degeneration (AMD). Those stress conditions increase reactive oxygen species (ROS) levels and oxidative stress, which can induce mitochondrial dysfunction and promote RPE cell death during retinal degeneration. We transplanted mitochondria, isolated from C2C12 cells, into cultured RPE cells, and RPE cell injury was induced by NaIO3 treatment. To evaluate the protective effect of mitochondrial transplantation, Annexin V/PI and cell viability assays were performed to measure the cell survival, and ROS levels were measured by flow cytometry to analyze cellular stress. To understand the underlying protective mechanism of mitochondrial transplantation, we measure expression of the antioxidant genes, mitochondrial fusion/fission markers, and mitophagy makers using qRT-PCR and Western blot methods. Mitochondrial transplantation reduced NaIO3-induced cell death and ROS levels, and antioxidant genes related to the Nrf2 pathway were upregulated, providing a protective effect against retinal damage. In addition, mitochondrial fusion was increased, whereas fission was decreased in the NaIO3 model. Furthermore, mitophagy was increased by mitochondrial transplantation, which could clear damaged mitochondria through a cellular protective pathway. In conclusion, mitochondrial transplantation could protect the RPE cells by maintaining mitochondrial homeostasis and promoting the antioxidant pathway via Nrf2 activation. This study suggests that mitochondrial transplantation could be a potential treatment option for improving AMD progress in the future.