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Myoung Sup Sim, Dongwook Lee, Keun-Young Kim, Robert Weinreb, Won-Kyu Ju; Effect of coenzyme Q10 on oxidative stress and mitochondrial DNA alteration in a mouse model of glaucoma. Invest. Ophthalmol. Vis. Sci. 2013;54(15):424.
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Oxidative stress and mitochondrial dysfunction have been implicated as important pathophysiological mechanisms in glaucomatous optic neuropathy. Coenzyme Q10 (CoQ10) 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-mediated retinal ganglion cell loss as well as preserves mitochondrial transcription factor A (Tfam) protein expression and mitochondrial DNA (mtDNA) content in the retina of a mouse model of glaucoma.
Pre-glaucomatous DBA/2J (D2) mice were fed with 1% CoQ10 and control diet daily for 6 month and intraocular pressure (IOP) in the eyes was measured monthly. RGC survival was measured by immunohistochemistry for Brn3a. Apoptotic pathway was assessed by Western blot for Bax and phosphorylated Bad (pBad). The protein expression levels of glial fibrillary acidic protein (GFAP), superoxide dismutase 2 (SOD2), heme oxgenase-1 (HO-1) or Tfam/oxidative phosphorylation (OXPHOS) complex were assessed by Western blot or immunohistochemistry. mtDNA content was measured by real-time PCR.
There were no significant differences for IOP and body weight between control diet- and 1% CoQ10-treated glaucomatous D2 mice at age of 10 months. In comparison with control diet-treated glaucomatous retina, CoQ10 diet promoted about 30% of RGC survival and prevented the upregulation of GFAP protein expression. CoQ10 diet significantly blocked the upregulation of SOD2 and HO-1 protein expression as well as decreased Bax protein expression, but increased pBad protein expression in glaucomatous D2 mouse retina. Importantly, CoQ10 diet preserved mtDNA content and Tfam/OXPHOS complex protein expression in glaucomatous D2 mouse retina.
Our results demonstrate that CoQ10 diet ameliorates RGC loss against oxidative stress by blocking Bax/Bad-mediated apoptotic pathway as well as preserves mtDNA content and Tfam/OXPHOS complex expression in glaucomatous retina. Based on these observations, CoQ10 diet may provide a promising therapeutic strategy against oxidative stress-mediated mitochondrial dysfunction in glaucomatous optic neuropathy.
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