RT Journal Article
SR Electronic
T1 Inhibition of mitochondrial fission preserves photoreceptors after retinal detachment
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 197467
DO 10.1101/197467
A1 Xiangjun She
A1 Xinmin Lu
A1 Tong Li
A1 Junran Sun
A1 Jian Liang
A1 Yuanqi Zhai
A1 Shiqi Yang
A1 Qing Gu
A1 Fang Wei
A1 Hong Zhu
A1 Fenghua Wang
A1 Xueting Luo
A1 Xiaodong Sun
YR 2017
UL http://biorxiv.org/content/early/2017/10/02/197467.abstract
AB 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.