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M Francesca Cordeiro, Eduardo M. Normando, Li Guo, Shereen Nizari; Topical CoQ10 Modifies Profile Of Different Phases Of Retinal Ganglion Cell Death In Experimental Glaucoma. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1643.
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We recently described a new methodology for quantifying different phases of RGC death in vivo as a method of tracking disease activity. The data suggested that the profile of RGC death was related to the stage of disease and its treatment. CoQ10 is a molecule that has been shown to have neuroprotective activity through its effects on the mitochondrial permeability transition pore. In this study, we investigate the effects of topical CoQ10 on the multiple phases of RGC death in an experimental model of glaucoma.
DA rats were randomly assigned to treatment with control (carrier) or CoQ10 0.1% eyedrops (Visufarma srl, Italy) 30 minutes before, and 1 hour and 1 week after IOP elevation using our established method. Animals were imaged at baseline, 1, 3 and 8 weeks after IOP elevation (at least n=6/treatment/time point), following intravitreal administration of IR-labelled annexin (Annexin V) and propidium iodide (PI) 2 hours beforehand. The magnitude of early (Annexin V positive) and late (Annexin V & PI positive) phase apoptosis, and necrosis (PI positive) was quantifiefd as previously described.
Our results confirmed that peak RGC apoptosis occurs 3 weeks after surgical induction of elevated IOP in this model, as we have previously shown. Furthermore, in untreated controls, there was a significant (p<0.05) increase in cells in late phase apoptosis compared to either necrosis or early phase apoptosis. Similarly, only a small proportion of RGCs were identified in early phase apoptosis (annexin V only) compared to late phase apoptosis (both annexin V and PI staining) at 3 weeks, although at 1 week there was significantly more late phase apoptosis than necrosis (p<0.05). CoQ10 apeared to significantly inhibit the development of RGC apoptosis at all time points in the OHT model (p<0.05). Furthermore, at 1 and 3 weeks CoQ10 significantly reduced the level of late apoptosis in RGCs (p<0.05).
These results show that CoQ10 0.1% significantly modifies the profile of phases of RGC death, and confirms that our methodology enables temporal resolution and quantification of the early and late phases of apoptosis and necrosis of single nerve cells. Furthermore, it suggests that CoQ10 targets apoptosis in vivo, and that it is active topically. We believe CoQ10 represents a promising neuroprotective topical treatment in glaucoma with clinical trials planned shortly.
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