Coenzyme Q10 ameliorates oxidative stress and prevents mitochondrial alteration in ischemic retinal injury

Abstract

Coenzyme Q10 (CoQ10) acts by scavenging reactive oxygen species for protecting neuronal cells against oxidative stress in neurodegenerative diseases. We tested whether a diet supplemented with CoQ10 ameliorates oxidative stress and mitochondrial alteration, as well as promotes retinal ganglion cell (RGC) survival in ischemic retina induced by intraocular pressure elevation. A CoQ10 significantly promoted RGC survival at 2 weeks after ischemia. Superoxide dismutase 2 (SOD2) and heme oxygenase-1 (HO-1) expression were significantly increased at 12 h after ischemic injury. In contrast, the CoQ10 significantly prevented the upregulation of SOD2 and HO-1 protein expression in ischemic retina. In addition, the CoQ10 significantly blocked activation of astroglial and microglial cells in ischemic retina. Interestingly, the CoQ10 blocked apoptosis by decreasing caspase-3 protein expression in ischemic retina. Bax and phosphorylated Bad (pBad) protein expression were significantly increased in ischemic retina at 12 h. Interestingly, while CoQ10 significantly decreased Bax protein expression in ischemic retina, CoQ10 showed greater increase of pBad protein expression. Of interest, ischemic injury significantly increased mitochondrial transcription factor A (Tfam) protein expression in the retina at 12 h, however, CoQ10 significantly preserved Tfam protein expression in ischemic retina. Interestingly, there were no differences in mitochondrial DNA content among control- or CoQ10-treated groups. Our findings demonstrate that CoQ10 protects RGCs against oxidative stress by modulating the Bax/Bad-mediated mitochondrial apoptotic pathway as well as prevents mitochondrial alteration by preserving Tfam protein expression in ischemic retina. Our results suggest that CoQ10 may provide neuroprotection against oxidative stress-mediated mitochondrial alterations in ischemic retinal injury.Electronic supplementary materialThe online version of this article (doi:10.1007/s10495-013-0956-x) contains supplementary material, which is available to authorized users.

Retinal proteomics of experimental glaucoma model reveal intraocular pressure‐induced mediators of neurodegenerative changes

“…Modulating mitochondrial integrity, such as by inducing DRP1 inhibition or CoQ 10 treatment, has been shown to rescue RGCs in glaucoma. 31,61,62 Mitochondrial dysfunction, in turn, affects the NAD/NADH levels and here we observed downregulation of certain key redox regulatory enzymes in response to high IOP exposure, such as aldehyde dehydrogenase, enolase, aldose reductase, acyl dehydrogenase, and phosphoglycerate dehydrogenase. We have previously reported downregulation of 13 subunits of the NADH dehydrogenase: ubiquinone oxidoreductase complex 1 in the human POAG, and these findings together may reflect a failure of the tissues to maintain redox homoeostasis in glaucoma.…”

Management of Glaucoma As a Neurodegenerative Disease

“…Many animal studies have provided promising results for Co-Q10's neuroprotective effects in glaucoma models; It has been demonstrated that intraocular and oral Co-Q10 reduces RGC apoptosis [49], and ameliorates oxidative stress mediated mitochondrial dysfunction in a rat OHT model [50]. Co-Q10 can also reduce damage from glutamate excitotoxity, and promote RGC survival by preserving optic nerve head axons in glaucomatous mice [51].…”

Modulation of the Isoprenoid/Cholesterol Biosynthetic Pathway During Neuronal Differentiation In Vitro

“…). Its end products (e.g., coenzyme Q10, prenyls, and cholesterol) are essential for neuronal function [Lee et al, ; Segatto et al, ; Villarroel‐Campos et al, ]: cholesterol, for example, is a key component of the myelin sheath and of neuronal membranes in axons, dendrites, and synapses [Orth and Bellosta, ]. It must be synthesized within the brain as the blood‐brain barrier prevents import of lipoproteins, but the cellular origin of the different pools in neurons are incompletely understood [Pfrieger and Ungerer, ; Segatto et al, ].…”