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bioRxiv · 10.1101/197467

Inhibition of mitochondrial fission preserves photoreceptors after retinal detachment

She, X.·Lu, X.·Li, T.·Sun, J.·Liang, J.·Zhai, Y.·Yang, S.·Gu, Q.·Wei, F.·Zhu, H.·Wang, F.·Luo, X.·Sun, X.
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Abstract

Photoreceptor degeneration is a leading cause of visual impairment worldwide. Separation of neurosensory retina from the underlying retinal pigment epithelium is a prominent feature preceding photoreceptor degeneration in a variety of retinal diseases. Although ophthalmic surgeries have been well developed to restore retinal structures, post-op patients usually experience progressive photoreceptor degeneration and irreversible vision loss that is incurable at present. Previous studies point to a critical role of mitochondria-mediated apoptotic pathway in photoreceptor degeneration, but the upstream triggers remain largely unexplored. In this study, we show that after experimental RD induction, photoreceptors activate dynamin-related protein 1 (Drp1)-dependent mitochondrial fission pathway and subsequent apoptotic cascades. Mechanistically, endogenous ROS is necessary for Drp1 activation in vivo and exogenous ROS insult is sufficient to activate Drp1-dependent mitochondrial fission in cultured photoreceptors. Accordingly, inhibition of Drp1 activity effectively preserves mitochondrial integrity and rescues photoreceptors. Collectively, our data delineates a ROS-Drp1-mitochondria axis that promotes photoreceptor degeneration in retinal diseased models.

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She, X., Lu, X., Li, T., Sun, J., Liang, J., Zhai, Y., Yang, S., Gu, Q., Wei, F., Zhu, H., Wang, F., Luo, X., Sun, X.. 2017-10-02. Inhibition of mitochondrial fission preserves photoreceptors after retinal detachment. https://doi.org/10.1101/197467

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