July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Mitochondria fission by Drp1 as the potential therapeutic target for retinal pigmented epithelial cell death
Author Affiliations & Notes
  • Tomohiro Yako
    Gifu Pharmaceutical Univercity,, Gifu, Gifu, Japan
  • Maho Nakamura
    Gifu Pharmaceutical Univercity,, Gifu, Gifu, Japan
  • Shinsuke Nakamura
    Gifu Pharmaceutical Univercity,, Gifu, Gifu, Japan
  • Masamitsu Shimazawa
    Gifu Pharmaceutical Univercity,, Gifu, Gifu, Japan
  • Hideaki Hara
    Gifu Pharmaceutical Univercity,, Gifu, Gifu, Japan
  • Footnotes
    Commercial Relationships   Tomohiro Yako, None; Maho Nakamura, None; Shinsuke Nakamura, None; Masamitsu Shimazawa, None; Hideaki Hara, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 1948. doi:
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      Tomohiro Yako, Maho Nakamura, Shinsuke Nakamura, Masamitsu Shimazawa, Hideaki Hara; Mitochondria fission by Drp1 as the potential therapeutic target for retinal pigmented epithelial cell death. Invest. Ophthalmol. Vis. Sci. 2019;60(9):1948.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose : The retinal pigmented epithelial (RPE) cell death and dysfunction are the characteristic lesions in the age-related macular degeneration (AMD) patients. These underlying mechanisms are not fully unknown. Interestingly, in RPE of non-exudative AMD the fragmented mitochondria are observed. Mitochondria fragmentation and cell death are caused by mitochondria fission. Especially, dynamin-related protein 1 (Drp1) plays a key role in mitochondria fission. However, the relationship between Drp1 and non-exudative AMD is almost unknown. The purpose of this study was to find the therapeutic target focusing on mitochondoria of RPE cell.

Methods : The human derived RPE cell line (ARPE-19) was seeded at density of 1.5x 105 cells/ml and oxidative stress was caused by adding H2O2 at 200 µM. A mitochondria division inhibitor 1 (Mdivi-1), known as Drp1 inhibitor, was added before 1 h adding H2O2 to analyze the protective effect against oxidative stress. We used Hoechst and propidium iodide staining and cell counting kit-8 to investigate the cell viability. Moreover we used JC-1 staining, reactive oxygen species (ROS) assay and immunostaining to investigate the protective effects for the mitochondria.

Results : Mdivi-1 treatment improved the cell viability against oxidative stress in a concentration-dependent manner, and its protective effect was indicated at 50 µM. Mdivi1 suppressed the ratio of damaged mitochondria. H2O2 significantly increased ROS production in RPE cell, and Mdivi-1 decreased it in concentration-dependent manner. Mdivi-1 treatment suppressed the mitochondria aggregation and the cytochrome c releasing from mitochondria induced by H2O2. These results showed that oxidative stress could cause releasing cytochrome c from mitochondria and induced apoptosis signaling activation. Taken together, Mdivi-1 had the protective effect against the cell apoptosis through inhibiting mitochondria fission.

Conclusions : These findings indicate that the mitochondria fission related with oxidative stress-induced RPE cell death, and inhibition of mitochondria fission could be one of novel therapeutic approaches for the disease attributed to RPE cell death.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.


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