Mitochondria-Targeted Plastoquinone Derivatives as Tools to Interrupt Execution of the Aging Program.
4. Age-Related Eye Disease. SkQ1 Returns Vision to Blind Animals

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V. V. Neroev¹, M. M. Archipova¹, L. E. Bakeeva², A. Zh. Fursova³, E. N. Grigorian⁴, A. Yu. Grishanova³, E. N. Iomdina¹, Zh. N. Ivashchenko¹, L. A. Katargina¹, I. P. Khoroshilova-Maslova¹, O. V. Kilina², N. G. Kolosova³, E. P. Kopenkin⁵, S. S. Korshunov², N. A. Kovaleva⁴, Yu. P. Novikova⁴, P. P. Philippov², D. I. Pilipenko², O. V. Robustova¹, V. B. Saprunova², I. I. Senin², M. V. Skulachev⁶, L. F. Sotnikova⁵, N. A. Stefanova³, N. K. Tikhomirova², I. V. Tsapenko¹, A. I. Shchipanova¹, R. A. Zinovkin², and V. P. Skulachev^2,6,7*

¹Helmholtz Moscow Research Institute of Eye Diseases, ul. Sadovaya-Chernogryazskaya 14/19, 105062 Moscow, Russia

²Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, Russia; fax: (495) 939-0338; E-mail: skulach@belozersky.msu.ru

³Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, pr. Lavrentieva 10, 630090 Novosibirsk, Russia

⁴Kol'tsov Institute of Developmental Biology, Russian Academy of Sciences, ul. Vavilova 26, 119991 Moscow, Russia

⁵Skryabin Moscow State Academy of Veterinary Medicine and Biotechnology, ul. Skryabina 23, 109472 Moscow, Russia

⁶Mitoengineering Center, Lomonosov Moscow State University, 119991 Moscow, Russia

⁷Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119899 Moscow, Russia

^* To whom correspondence should be addressed.

Received December 29, 2007; Revision received August 15, 2008

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Mitochondria-targeted cationic plastoquinone derivative SkQ1 (10-(6´-plastoquinonyl) decyltriphenylphosphonium) has been investigated as a potential tool for treating a number of ROS-related ocular diseases. In OXYS rats suffering from a ROS-induced progeria, very small amounts of SkQ1 (50 nmol/kg per day) added to food were found to prevent development of age-induced cataract and retinopathies of the eye, lipid peroxidation and protein carbonylation in skeletal muscles, as well as a decrease in bone mineralization. Instillation of drops of 250 nM SkQ1 reversed cataract and retinopathies in 3-12-month-old (but not in 24-month-old) OXYS rats. In rabbits, experimental uveitis and glaucoma were induced by immunization with arrestin and injections of hydroxypropyl methyl cellulose to the eye anterior sector, respectively. Uveitis was found to be prevented or reversed by instillation of 250 nM SkQ1 drops (four drops per day). Development of glaucoma was retarded by drops of 5 µM SkQ1 (one drop daily). SkQ1 was tested in veterinarian practice. A totally of 271 animals (dogs, cats, and horses) suffering from retinopathies, uveitis, conjunctivitis, and cornea diseases were treated with drops of 250 nM SkQ1. In 242 cases, positive therapeutic effect was obvious. Among animals suffering from retinopathies, 89 were blind. In 67 cases, vision returned after SkQ1 treatment. In ex vivo studies of cultivated posterior retina sector, it was found that 20 nM SkQ1 strongly decreased macrophagal transformation of the retinal pigmented epithelial cells, an effect which might explain some of the above SkQ1 activities. It is concluded that low concentrations of SkQ1 are promising in treating retinopathies, cataract, uveitis, glaucoma, and some other ocular diseases.

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KEY WORDS: mitochondria, antioxidants, retinopathies, cataract, uveitis, glaucoma

DOI: 10.1134/0006297908120043

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