Changes in Mitochondrial Morphology and Mitochondrial Fission/Fusion Gene Expression in Retinal Pigment Epithelial Cells During Oxidative Stress

Abstract

Age-related macular degeneration (AMD) represents a serious impairment for the elderly. Because the pathogenesis of AMD has not been completely defined, the available therapeutic treatments are not ideal. Retinal pigment epithelial (RPE) cells are essential for photoreceptor cell maintenance and survival; however, the mechanisms underlying RPE cell damage and AMD remains to be elucidated. It is known that abnormal mitochondrial gene expression causes mitochondrial dysfunction, induces cell damage, and results in disease. In this study, ARPE-19 cells were treated with different concentrations of H2O2. It was found that excessive H2O2 concentration resulted in significant contraction of ARPE-19 cells and increased cell death, and destruction of mitochondrial structure as well as membrane and crest. RT-PCR results showed that decreased expression of the Fis1 gene was evident in H2O2-treated cells. There were no significant differences observed among the different H2O2 concentration groups. The expression of the fission genes, MTP18 and Dnmp1, and the fusion genes, Mnf1 and Mnf2, was not significantly different. Real-time PCR results revealed that the expression of the Fis1 gene decreased concomitantly with different concentrations of H2O2, whereas the expression of the Mfn2 gene increased by treatment with 200 μMH2O2. There were no significant differences in the expression of the other genes. These results indicate that abnormal expression of the mitochondrial Fis1 fission gene, and the Mfn2 fusion gene caused mitochondrial dysfunction in ARPE-19 cells. This indicates that the imbalance of mitochondrial dynamics may contribute to cell death in an oxidative stress environment.