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Dongwook Lee, Keun-Young Kim, Won-Kyu Ju; Coenzyme Q10 ameliorates oxidative stress and preserves mitochondrial transcription factor A in ischemic retinal injury. Invest. Ophthalmol. Vis. Sci. 2013;54(15):423.
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Oxidative stress has been linked to mitochondrial dysfunction in retinal ischemia and optic neuropathies including glaucoma. Coenzyme Q10 (CoQ10), an essential cofactor of the electron transport chain, acts by scavenging reactive oxygen species for protecting neuronal cells against oxidative stress in neurodegenerative diseases. Here, we tested whether CoQ10 diet ameliorates oxidative stress and mitochondrial dysfunction, as well as promotes retinal ganglion cell (RGC) survival in ischemic retinal injury.
Pre-ischemic C57BL/6 mice were fed with 1% CoQ10 daily for 1 week and then transient ischemia was induced by acute intraocular pressure elevation. RGC survival was measured by immunohistochemstry for Brn3a. Apoptotic pathway was assessed by Western blot for Bax and phosphorylated Bad (pBad). The expression levels of glial fibrillary acidic protein (GFAP), Iba1, superoxide dismutase 2 (SOD2), heme oxgenase 1 (HO-1) or mitochondrial transcription factor A (Tfam) were assessed by Western blot or immunohistochemistry.
CoQ10 diet significantly promoted RGC survival at 2 weeks after ischemia. At 12 hours, the upregulation of GFAP and Iba1 protein expression was blocked in ischemic retina treated with CoQ10 diet. Further, we observed that CoQ10 diet significantly prevented the upregulation of Bax protein expression but increased pBad protein expression in ischemic retina at 12 hours. In ischemic retina treated with control diet, the expression level of SOD2 and Tfam protein was peaked at 12 hours and decreased at 24 hours. Importantly, CoQ10 diet blocked the upregulation of SOD2 and HO-1 protein expression, as well as Tfam protein expression in ischemic retina at 12 hours.
Our findings demonstrate that CoQ10 diet ameliorates RGC loss against oxidative stress by blocking Bax/Bad-mediated apoptotic pathway as well as preserves Tfam/OXPHOS complex expression in ischemic retina. Therefore, we suggest that CoQ10 diet may be a useful neuroprotective strategy against oxidative stress-mediated mitochondrial dysfunction in ischemic retinal injury.
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