Satoshi Yokota1, Yuji Takihara2, Shogo Arimura2, Seiji Miyake2, Yoshihiro Takamura2, Nagahisa Yoshimura3, Masaru Inatani2. 1. Department of Ophthalmology Faculty of Medical Science, University of Fukui, Fukui, Japan 2Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan. 2. Department of Ophthalmology Faculty of Medical Science, University of Fukui, Fukui, Japan. 3. Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Abstract
PURPOSE: Axonal damage precedes retinal ganglion cell (RGC) apoptosis in glaucomatous optic neuropathy. Because mitochondria in RGC axons are damaged before cell death, we examined axonal mitochondrial transport dynamics after axonal injury. METHODS: Mitochondria in rat-cultivated RGCs were stained with rhodamine 123. After axonal injury induced using a laser microdissection system, axonal transport was evaluated by time-lapse imaging. The RGC apoptosis was detected using ethidium homodimer-1 on day 3 after axonal injury. RESULTS: The rate of stationary mitochondria in RGC axons significantly increased from 37.6% before axonal injury to 70.6% at 5 minutes (P < 0.001) and 63.6% at 18 hours (P < 0.001) after axonal injury. The mean axonal mitochondrial transport velocity in RGCs transiently deteriorated from 0.48 ± 0.01 μm/s before axonal injury to 0.37 ± 0.02 μm/s at 5 minutes after axonal injury (P < 0.001). However, 23.5% of RGCs showed recovered axonal transport velocity at 18 hours after injury. On day 3 after axonal injury, RGCs with the recovery of axonal transport did not undergo apoptosis, whereas 69.2% of RGCs without the recovery of axonal transport underwent apoptosis (P = 0.029). CONCLUSIONS: Axonal injury disrupts mitochondrial transport in RGC axons. Irreversible decreased axonal mitochondrial transport velocity may be useful to predict RGC apoptosis after axonal injury.
PURPOSE: Axonal damage precedes retinal ganglion cell (RGC) apoptosis in glaucomatous optic neuropathy. Because mitochondria in RGC axons are damaged before cell death, we examined axonal mitochondrial transport dynamics after axonal injury. METHODS: Mitochondria in rat-cultivated RGCs were stained with rhodamine 123. After axonal injury induced using a laser microdissection system, axonal transport was evaluated by time-lapse imaging. The RGC apoptosis was detected using ethidium homodimer-1 on day 3 after axonal injury. RESULTS: The rate of stationary mitochondria in RGC axons significantly increased from 37.6% before axonal injury to 70.6% at 5 minutes (P < 0.001) and 63.6% at 18 hours (P < 0.001) after axonal injury. The mean axonal mitochondrial transport velocity in RGCs transiently deteriorated from 0.48 ± 0.01 μm/s before axonal injury to 0.37 ± 0.02 μm/s at 5 minutes after axonal injury (P < 0.001). However, 23.5% of RGCs showed recovered axonal transport velocity at 18 hours after injury. On day 3 after axonal injury, RGCs with the recovery of axonal transport did not undergo apoptosis, whereas 69.2% of RGCs without the recovery of axonal transport underwent apoptosis (P = 0.029). CONCLUSIONS:Axonal injury disrupts mitochondrial transport in RGC axons. Irreversible decreased axonal mitochondrial transport velocity may be useful to predict RGC apoptosis after axonal injury.
Authors: Elizabeth C Kimball; Mary E Pease; Matthew R Steinhart; Ericka N Oglesby; Ian Pitha; Cathy Nguyen; Harry A Quigley Journal: Exp Eye Res Date: 2017-04-14 Impact factor: 3.467
Authors: Sahil H Shah; Lucio M Schiapparelli; Yuanhui Ma; Satoshi Yokota; Melissa Atkins; Xin Xia; Evan G Cameron; Thanh Huang; Sarah Saturday; Catalina B Sun; Cara Knasel; Seth Blackshaw; John R Yates; Hollis T Cline; Jeffrey L Goldberg Journal: Elife Date: 2022-03-08 Impact factor: 8.140