Mitochondria-targeted antioxidant SkQ1 reverses glaucomatous lesions in rabbits

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Elena N. Iomdina¹, Inna P. Khoroshilova- Maslova¹, Olga V. Robustova¹, Olga A. Averina², Nadezhda A. Kovaleva³, Gjumrakch Aliev^4,5, V. Prakash Reddy⁶, Andrey A. Zamyatnin Jr.^3,7, Maxim V. Skulachev⁸, Ivan I. Senin^3,9, Vladimir P. Skulachev^2,3,*

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¹ Moscow Helmholtz Research Institute of Eye Diseases, Moscow, Russia

² Lomonosov Moscow State University, Faculty of Bioengineering and Bioinformatics, Moscow 119992, Russia

³ Lomonosov Moscow State University, Belozersky Institute of Physico-Chemical Biology, Moscow 119992, Russia

⁴ GALLY International Biomedical Research Consulting LLC, San Antonio, Texas, 78229, USA

⁵ School of Health Science and Healthcare Administration, The University of Atlanta, Johns Creek, USA

⁶ Department of Chemistry, Missouri University of Science and Technology, Rolla, MO 65409, USA

⁷ Sechenov First Moscow State Medical University, Institute of Molecular Medicine, Moscow 119991, Russia

⁸ Lomonosov Moscow State University, Biological Faculty, Moscow 119991, Russia

⁹ Lomonosov Moscow State University, Institute of Mitoengineering, Moscow 119992, Russia

Front. Biosci. (Landmark Ed) 2015, 20(5), 892–901; https://doi.org/10.2741/4343

Published: 1 January 2015

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Abstract

Glaucoma is the main cause of irreversible blindness worldwide. This disease is characterized by apoptosis of retinal ganglion cells (RGC) and visual field loss that seems to be related to elevated intraocular pressure (IOP). Several lines of evidences have implicated the crucial role of mitochondrial dysfunction in the pathogenesis of glaucoma. Increased mitochondrial oxidative stress in RGC may underlie or contribute to susceptibility of RGC to apoptosis. In our work we (i) designed a rabbit model of chronic, moderately elevated IOP for studying glaucoma and (ii) demonstrated efficacy of mitochondria-targeted antioxidant SkQ1 as a tool to reverse several traits of experimental glaucoma induced by a series of injections of hydroxypropylmethylcellulose (HPMC) to the anterior chamber of the rabbit eye. It is shown that 6 months instillations of drops of 0.2.5-5 μM solution of SkQ1 normalize IOP and eye hydrodynamics and abolish an increase in lens thickness that accompanies glaucoma.

Keywords

Glaucoma

Rabbit Model

Mitochondria-Targeted Antioxidant

Reversal Of Lesions

SkQ1

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