Literature DB >> 19120017

Mitochondria-targeted plastoquinone derivatives as tools to interrupt execution of the aging program. 4. Age-related eye disease. SkQ1 returns vision to blind animals.

V V Neroev1, M M Archipova, L E Bakeeva, A Zh Fursova, E N Grigorian, A Yu Grishanova, E N Iomdina, Zh N Ivashchenko, L A Katargina, I P Khoroshilova-Maslova, O V Kilina, N G Kolosova, E P Kopenkin, S S Korshunov, N A Kovaleva, Yu P Novikova, P P Philippov, D I Pilipenko, O V Robustova, V B Saprunova, I I Senin, M V Skulachev, L F Sotnikova, N A Stefanova, N K Tikhomirova, I V Tsapenko, A I Shchipanova, R A Zinovkin, V P Skulachev.   

Abstract

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 microM 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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Year:  2008        PMID: 19120017     DOI: 10.1134/s0006297908120043

Source DB:  PubMed          Journal:  Biochemistry (Mosc)        ISSN: 0006-2979            Impact factor:   2.487


  39 in total

Review 1.  Animal models of age related macular degeneration.

Authors:  Mark E Pennesi; Martha Neuringer; Robert J Courtney
Journal:  Mol Aspects Med       Date:  2012-06-15

2.  Rat retinal transcriptome: effects of aging and AMD-like retinopathy.

Authors:  Oyuna S Kozhevnikova; Elena E Korbolina; Nikita I Ershov; Natalia G Kolosova
Journal:  Cell Cycle       Date:  2013-05-06       Impact factor: 4.534

3.  Novel mitochondria-targeted antioxidants: plastoquinone conjugated with cationic plant alkaloids berberine and palmatine.

Authors:  Konstantin G Lyamzaev; Antonina V Pustovidko; Ruben A Simonyan; Tatyana I Rokitskaya; Lidia V Domnina; Olga Yu Ivanova; Inna I Severina; Natalia V Sumbatyan; Galina A Korshunova; Vadim N Tashlitsky; Vitaly A Roginsky; Yuriy N Antonenko; Maxim V Skulachev; Boris V Chernyak; Vladimir P Skulachev
Journal:  Pharm Res       Date:  2011-06-14       Impact factor: 4.200

4.  Ameliorative effects of SkQ1 eye drops on cataractogenesis in senescence-accelerated OXYS rats.

Authors:  Yuliya V Rumyantseva; Elena I Ryabchikova; Anjela Z Fursova; Nataliya G Kolosova
Journal:  Graefes Arch Clin Exp Ophthalmol       Date:  2014-09-30       Impact factor: 3.117

5.  Application of quantitative trait locus mapping and transcriptomics to studies of the senescence-accelerated phenotype in rats.

Authors:  Elena E Korbolina; Nikita I Ershov; Leonid O Bryzgalov; Natalia G Kolosova
Journal:  BMC Genomics       Date:  2014-12-19       Impact factor: 3.969

6.  The mitochondria-targeted antioxidant SkQ1 restores αB-crystallin expression and protects against AMD-like retinopathy in OXYS rats.

Authors:  Natalia A Muraleva; Oyuna S Kozhevnikova; Anna A Zhdankina; Natalia A Stefanova; Tatyana V Karamysheva; Anzhella Z Fursova; Nataliya G Kolosova
Journal:  Cell Cycle       Date:  2014       Impact factor: 4.534

7.  Penetrating cation/fatty acid anion pair as a mitochondria-targeted protonophore.

Authors:  Fedor F Severin; Inna I Severina; Yury N Antonenko; Tatiana I Rokitskaya; Dmitry A Cherepanov; Elena N Mokhova; Mikhail Yu Vyssokikh; Antonina V Pustovidko; Olga V Markova; Lev S Yaguzhinsky; Galina A Korshunova; Nataliya V Sumbatyan; Maxim V Skulachev; Vladimir P Skulachev
Journal:  Proc Natl Acad Sci U S A       Date:  2009-12-18       Impact factor: 11.205

8.  Mitochondria-targeted antioxidant SkQ1 inhibits age-dependent involution of the thymus in normal and senescence-prone rats.

Authors:  Lidia A Obukhova; Vladimir P Skulachev; Natalia G Kolosova
Journal:  Aging (Albany NY)       Date:  2009-04-22       Impact factor: 5.682

9.  Chain-breaking antioxidant activity of reduced forms of mitochondria-targeted quinones, a novel type of geroprotectors.

Authors:  Vitaly A Roginsky; Vadim N Tashlitsky; Vladimir P Skulachev
Journal:  Aging (Albany NY)       Date:  2009-05-12       Impact factor: 5.682

10.  Mitochondrial superoxide: a key player in Alzheimer's disease.

Authors:  Cynthia A Massaad; Robia G Pautler; Eric Klann
Journal:  Aging (Albany NY)       Date:  2009-09-14       Impact factor: 5.682

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