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Laura Belen, Kortni Violette, Christopher Schillo, Andy Whitlock, Anton Petrov; Evaluation of the effects of SkQ1 in Ora’s rabbit anterior chamber paracentesis model. Invest. Ophthalmol. Vis. Sci. 2016;57(12):5414.
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© ARVO (1962-2015); The Authors (2016-present)
SkQ1 is a novel compound and powerful antioxidant that accumulates in mitochondria where it is reduced and regenerated making it a potentially effective agent for treatment of ocular diseases associated with oxidative stress, lipid and protein peroxidation in the inner membrane of mitochondria. Ora’s anterior chamber paracentesis model (ACP) induces the release of pro-inflammatory proteins and prostaglandin E2 (PEG2) into the aqueous humor through the breakdown of the blood-aqueous barrier. The purpose of this study was to test Mitotech’s ophthalmic formulation of SkQ1 for its ability to reduce acute inflammation using this clinical model.
24 New Zealand White Rabbits were randomly assigned to either: 1.) Vehicle (0 µg/mL), 2.) SkQ1 (4.7µg/mL), 3.) Bromfenac (0.09%), 4.) SkQ1 (15.5µg/mL). Animals were evaluated via slit-lamp to identify fibrin & flare prior to the first dose of the study, prior to ACP 1, and prior to ACP 2. Animals received 4 doses daily, two days prior to ACP. On the day of ACP, animals received 4 doses over 180-mins and then 100µL of aqueous was removed (ACP 1). Animals received 3 doses within 90-mins following ACP 1 and the remaining aqueous was removed (ACP 2). One-way ANOVA was used to compare the endpoints (clinical evaluation, total protein, and PGE2) between the experimental and control groups.
Fibrin and flare scores were significantly reduced for both groups of SkQ1 (p<0.05) and Bromfenac (p<0.001) at ACP 2 compared to vehicle. Total protein was significantly lower in both SkQ1 groups (4.7µg/mL and 15.5µg/mL) at ACP 2 compared to vehicle (p<0.01 and p<0.001, respectively) with 15.5µg/mL showing a lower response than 4.7µg/mL. Significant differences were found in the % change in total protein from ACP 1 to ACP 2 between both groups of SkQ1 (4.7µg/mL and 15.5µg/mL) compared to vehicle (p<0.05 and p<0.001, respectively) with Bromfenac significantly lower than vehicle (p<0.0001). Bromfenac showed a significant decrease in PGE2 levels compared to vehicle at ACP2 (p<0.05), but neither group of SkQ1 were significantly reduced.
SkQ1 can reduce inflammation both clinically and biochemically in this model of inflammation. SkQ1 reduces total protein levels in the anterior chamber in a dose-dependent manner. Although there was a trend toward reduction, neither SkQ1 group significantly reduced PGE2 level in the aqueous humor.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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