%0 Journal Article %A Xiangjun She %A Xinmin Lu %A Tong Li %A Junran Sun %A Jian Liang %A Yuanqi Zhai %A Shiqi Yang %A Qing Gu %A Fang Wei %A Hong Zhu %A Fenghua Wang %A Xueting Luo %A Xiaodong Sun %T Inhibition of mitochondrial fission preserves photoreceptors after retinal detachment %D 2017 %R 10.1101/197467 %J bioRxiv %P 197467 %X 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. %U https://www.biorxiv.org/content/biorxiv/early/2017/10/02/197467.full.pdf